PEDIATRICS Vol. 120 No. 3 September 2007, pp. 509-518 (doi:10.1542/peds.2007-0775)
ARTICLE |
Continuous Positive Airway Pressure Therapy for Infants With Respiratory Distress in Non–Tertiary Care Centers: A Randomized, Controlled Trial
a Northern Sydney Central Coast Area Health Service, Gosford Hospital, Gosford, Australia
b Department of Paediatrics
c New South Wales Pregnancy and Newborn Services Network, University of Sydney, Camperdown, Australia
d Mother and Babies Research Centre, Hunter Medical Research Institute, Newcastle, Australia
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONAPPENDIX: MANAGEMENT GUIDELINESREFERENCES |
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OBJECTIVE. Our objective was to determine whether continuous positive airway pressure therapy would safely reduce the need for up-transfer of infants with respiratory distress from nontertiary centers.
METHODS. We randomly assigned 300 infants at >30 weeks of gestation with respiratory distress to receive either Hudson prong bubble continuous positive airway pressure therapy or headbox oxygen treatment (standard care). The primary end point was "up-transfer or treatment failure." Secondary end points included death, length of nursery stay, time receiving oxygen therapy, cost of care, and other measures of morbidity.
RESULTS. Of 151 infants who received continuous positive airway pressure therapy, 35 either were up-transferred or experienced treatment failure, as did 60 of the 149 infants given headbox oxygen treatment. There was no difference in the length of stay or the duration of oxygen treatment. For every 6 infants treated with continuous positive airway pressure therapy, there was an estimated cost saving of $10000. Pneumothorax was identified for 14 infants in the continuous positive airway pressure group and 5 in the headbox group. There was no difference in any other measure of morbidity or death.
CONCLUSIONS. Hudson prong bubble continuous positive airway pressure therapy reduces the need for up-transfer of infants with respiratory distress in nontertiary centers. There is a clinically relevant but not statistically significant increase in the risk of pneumothorax. There are significant benefits associated with continuous positive airway pressure use in larger nontertiary centers.
Key Words: continuous positive airway pressure • respiratory insufficiency • infant • newborn • neonatal intensive care • oxygen inhalation therapy • transportation of patients
Abbreviations: CPAP—continuous positive airway pressure • SCN—special-care nursery • NTC—nontertiary center • FIO2—fraction of inspired oxygen
Each year, 
13000 infants with respiratory distress are admitted to special-care nurseries (SCNs) in Australian nontertiary centers (NTCs). Approximately 500 are up-transferred to a NICU.1–3 Transferring an infant has significant emotional and financial implications,4 and many infants undergo invasive procedures during transfer to ensure their safety during the transfer.5
NTCs usually provide respiratory support through headbox oxygen treatment while waiting for clinical improvement. Respiratory support in NICUs, however, often commences with continuous positive airway pressure (CPAP) treatment.6 CPAP is thought to assist through the recruitment of alveoli and the increasing of functional residual capacity.7,8 CPAP reduces the work of breathing and may also conserve surfactant.9,10 A Cochrane review of any form of continuous distending pressure versus headbox treatment concluded that death or the need for any assisted ventilation is reduced (relative risk: 0.66; 95% confidence interval: 0.51–0.87).11 The review also concluded that the applicability of the results to current practice is difficult to assess, given the changes in management that have occurred since the 1970s when the trials were completed. Comparative data from 8 tertiary centers in the United States showed a lower incidence of chronic lung disease in low birth weight infants in a NICU that used nasal-prong CPAP treatment.12 Similar results were found in an interhospital comparison13 and in New Zealand in a before/after study.14
Data show an increase in the use of CPAP therapy for infants with respiratory distress in Australian and New Zealand NICUs.6,15 CPAP treatment is also in routine use in some NTCs in Scandinavia16 and New Zealand.17 Although no evidence has been published to demonstrate the benefit of CPAP therapy in NTCs, a nationwide survey of NTCs showed that CPAP therapy in some form was being used in 24 (17%) of 143 centers, with an additional 38% considering commencing its use.6 We conducted a trial to assess whether the use of CPAP therapy for infants with respiratory distress typically treated in NTCs would reduce the number of transfers to a NICU.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX: MANAGEMENT GUIDELINESREFERENCES |
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Study Design
The study was a multicenter, randomized, clinical trial involving 6 higher-level nurseries, equivalent to American Academy of Pediatrics nursery level IIb,18 between August 2002 and June 2006. The University of Sydney and each hospital's human ethics committee approved the study. Informed consent was obtained as close as possible to the time of admission to the nursery, to minimize delays between eligibility, randomization, and commencement of CPAP therapy.
The participating nurseries typically provide planned delivery and care for infants at >32 weeks of gestation but may provide ongoing care for unplanned deliveries at 31 to 32 weeks. The nurseries all had 24-hour pediatric registrar coverage, similar to senior resident/fellow coverage in the United States, and ensured that clinical staff members had practical and theoretical training in the use of CPAP therapy before commencement of the study. Training included education sessions, written information, and two 1-day conferences on CPAP treatment. A core group of nursing staff members from each center worked for 2 days at a NICU caring for infants receiving CPAP therapy. This provided practical, "hands-on" experience in commencing CPAP treatment, changing prongs, and providing care for infants receiving CPAP therapy.
The design and running of the trial were overseen by a steering committee with medical and nursing representatives from each center, representatives from the newborn emergency transport service, 2 neonatologists, and the research coordinator. This committee met every 3 months, enabling close monitoring of the trial in each of the centers. A decision guidelines document (see "Appendix") was created to ensure integrity of the trial and safety for the infants while allowing all other decisions to be made by the pediatricians in the usual way. The document included information on issues such as eligibility, the obtaining of consent, the outcome criteria, and the use of oxygen and saturation targets. It recommended that a chest radiograph be obtained as soon as infants were eligible, aiming to ensure that the commencement of CPAP therapy not be delayed. Recommendations were also made regarding the timing and obtaining of blood gas samples. All other management decisions, including the use of intravenous fluids and antibiotics, the commencement of feedings, and the use of investigations, were made by the team caring for the infant, led by the pediatrician in charge.
Participants
The study population included all infants <24 hours of age with clinical signs of respiratory distress (recession, grunt, nasal flare, and/or tachypnea) who required >30% oxygen in a headbox to maintain oxygen saturation levels of 
94% for >30 minutes. Infants were excluded if they were born at <31 weeks of gestation, weighed <1200 g (10th percentile at 31 weeks), had a 5-minute Apgar score of <4, or were thought to have a cardiac cause for their respiratory distress. Infants could also be excluded if the pediatrician deemed the child too sick for the study. For multiple births, only the first sibling to meet the criteria was eligible.
Study Protocol
Randomization was performed by computer at the National Health and Medical Research Council Clinical Trials Centre, stratified according to gestational age (31–33 weeks, 34–36 weeks, or term) and hospital. Infants assigned randomly to the headbox oxygen group continued to receive respiratory support in this way. Infants assigned to the CPAP group started treatment as soon as practical after randomization.
CPAP treatment was uniform throughout all hospitals, performed with a bubble CPAP delivery system for infants (BC151; Fisher and Paykel Healthcare, Auckland, New Zealand) at a pressure of 6 cm of water. Infant nasal CPAP cannulae (Hudson RCI, Temecula, CA) were held in place by using a proprietary CPAP hat (CPAP Cap Systems, Canberra, Australia). Humidified oxygen was provided at a flow rate of 8 to 10 L/min. Fraction of inspired oxygen (FIO2) values were adjusted to target saturations of 94% to 96% for both groups. Saturation oximeters used in each nursery were identical for the 2 groups. Observations were recorded at least hourly.
Primary and Secondary Outcomes
"Up-transfer or treatment failure" was the primary outcome of this trial. End points for treatment failure were developed by the steering committee and specified a priori. The decision to up-transfer could be made before an infant reached treatment failure criteria, after consultation with a tertiary service, which allowed pediatricians to use their clinical judgment. The 3 parameters of treatment failure were FIO2 (60% for the headbox group or 50% for the CPAP group), carbon dioxide level, and pH (CO2 levels of >60 mm Hg or pH of <7.25 in 2 successive gas samples 1 hour apart). Failure occurred if any 1 of these 3 criteria was met. Different oxygen thresholds were used for the headbox and CPAP groups because it was agreed by the members of the steering committee that, at a specific FIO2, an infant receiving CPAP therapy is likely to have a more-serious underlying illness than an infant receiving headbox oxygen treatment. The guidelines recommended a blood gas analysis within 2 hours of the infant becoming eligible, repeated between 1 and 4 hours later as clinically indicated if the CO2 level was >60 mm Hg or the pH was <7.25.
Nursery length of stay was calculated from the time of first admission until discharge, including time spent in the NICU or other SCNs. The length of oxygen treatment was calculated from the time of randomization and included all times of oxygen therapy at any center.
Costs in Australian dollars were calculated for both groups. Included were the following: disposable CPAP equipment, including caps, prongs, and bubble CPAP delivery system; daily hospital cost for an infant in a SCN or a NICU in New South Wales (median lengths of stay in SCNs and NICUs were used for each group of infants)19; ambulance costs for transfer by road (assumed round trip of 100 km); and ambulance costs for transfer by helicopter (assumed time of 2 hours).20 Because only some mothers required transfer and some infants required back-transfer, a percentage of the average costs for these transfers was calculated on the basis of the rates found in the trial.
Measures of morbidity included oxygen at 28 days of age, pneumothorax, intraventricular hemorrhage, use of inotropes, and ulceration of the nares. Any event that required urgent (within 10 minutes) medical attention was recorded. All adverse events were presented to an independent safety committee, which met every 6 months.
Statistical Analyses
With power of 80% and a type I error rate of .05, we calculated that 304 infants would be required in each group (608 total) to reduce the up-transfer or failure rate from an assumed rate of 15% to 7.5% (relative reduction: 0.5). An interim analysis, using an asymmetric approach,21 took place as planned at the end of September 2004, after the recruitment of 139 infants. It became apparent that the underlying rate of up-transfer or treatment failure (28%) was much higher than assumed; therefore, the sample size was revised at that point to 144 infants in each group. Because an interim analysis had been conducted on the main end point (up-transfer or treatment failure), a type 1 error rate of .03 was used in the final analysis. Other end points were not examined in the interim analysis and thus were assessed by using .05. Data entry and checking were conducted by the research coordinator, and all analyses were performed by Dr Buckmaster.
Differences in categorical variables were analyzed by using Fisher's exact test. The Mann-Whitney U test was used for nonparametric data. The primary analysis was conducted according to the intention to treat by using SPSS 11.5.0 (SPSS, Chicago, IL). All P values are 2-sided.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX: MANAGEMENT GUIDELINESREFERENCES |
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Of 1899 infants requiring oxygen who were admitted to participating nurseries during the trial, 63 were excluded for subjective reasons, including 39 who were deemed to be "too sick" and 13 who were thought to have had a cardiac cause (Fig 1). The 1477 infants with respiratory distress who did not meet eligibility criteria were supported in the usual way. CPAP therapy was not offered outside the trial.
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All 300 infants assigned randomly were monitored to discharge. The baseline characteristics of the mothers and infants at birth were similar (Table 1). No infant received surfactant before randomization or before the infant had met failure criteria or had been up-transferred.
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CPAP treatment commenced a median of 70 minutes after eligibility (interquartile range: 45–119 minutes), which was mostly attributable to delays in randomization. The primary and secondary outcomes for the 2 groups are shown in Table 2.
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CPAP therapy reduced the frequency of up-transfer or treatment failure significantly. In the CPAP group, 35 (23%) of the 151 infants were either up-transferred or failed treatment, compared with 60 (40%) of the 149 infants assigned to the headbox group (odds ratio: 0.45; 95% confidence interval: 0.27–0.74; P = .002). Up-transfer with or without treatment failure took place for 34 infants (23%) from the CPAP group, compared with 54 infants (36%) from the headbox group (odds ratio: 0.51; 95% confidence interval: 0.31–0.89; P = .01). CPAP therapy also reduced treatment failure significantly, from 47 infants (32%) assigned to headbox treatment to 30 infants (20%) assigned to CPAP treatment (odds ratio: 0.54; 95% confidence interval: 0.32–0.91; P = .03).
The cost of transferring an infant who experienced failure of headbox oxygen treatment ranged from $25890 to $30107, depending on whether road ambulance (58 infants, 66%) or helicopter (30 infants, 34%) was used. The average cost of transferring the mother was $262, and this occurred in 61% of infant transfers. The average cost of back-transferring the infant was $434, and this occurred in 78% of infant transfers. By using the number needed to treat for the primary outcome (up-transfer or treatment failure), 6 infants would need to be treated with CPAP to avoid 1 transfer. On the basis of the average costs and the percentages that occurred in this study, a cost saving of approximately $10000 would accrue for every 6 infants treated with CPAP.
The number of infants who had pneumothorax was 14 in the CPAP group, compared with 5 in the headbox group (P = .06). A chest drain was placed for 9 infants in the CPAP group and 3 infants in the headbox group (P = .14). All of the infants treated with a chest drain were transferred. One additional pneumothorax is created for every 17 infants treated with CPAP. There were no significant differences between the 2 groups with respect to death or any of the other adverse events measured (Table 3).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX: MANAGEMENT GUIDELINESREFERENCES |
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This large, randomized, controlled trial showed that CPAP therapy could reduce the up-transfer rate for infants with respiratory distress in large NTCs. For every 6 infants treated with CPAP, 1 less would be transferred or fail treatment. The outcome of up-transfer was selected specifically for its clinical importance to infants and their families, and the outcome of treatment failure was chosen both to minimize bias and to ensure that infants were not being maintained in the nursery inappropriately. This is the largest randomized trial of CPAP therapy in infants with respiratory distress and the only one to be reported in this setting.
The oxygen failure criterion was intentionally set at a lower level for CPAP treatment for safety reasons, with the assumption that an infant receiving CPAP therapy would be sicker at any given FIO2 requirement. With data for the highest recorded FIO2, if 50% was used as the cutoff value for failure in the headbox group, then the number of infants who experienced treatment failure in this group increased from 47 (32%) to 69 (46%).
Three randomized trials compared headbox oxygen therapy with CPAP therapy for the treatment of respiratory distress syndrome.11 Comparisons of their results with those of this study are difficult, because those studies all took place in NICUs in the 1970s before the routine use of surfactant and prenatal steroid therapy. The infants in those studies had respiratory distress syndrome, were smaller, were born at a lower gestational age, and were more severely ill (>60% oxygen before randomization). In 2002, a randomized trial in the United Kingdom comparing headbox oxygen therapy with CPAP therapy to prevent ventilation for infants born at 29 to 34 weeks of gestation was ceased because of insufficient numbers (R. D. Webb, MBBS, written communication, 2006).
The optimal timing for commencing CPAP therapy in this clinical setting is not known. Infants in the current trial were eligible for CPAP treatment at a median age of 2 hours but, because of delays, did not commence therapy until a median age of 4 hours (interquartile range: 146–395 minutes). Without the need for consent and randomization, CPAP treatment could have commenced at a median age of 165 minutes, which, if CPAP is surfactant-sparing, might have led to an even greater benefit. Although initiation of CPAP therapy at the first sign of respiratory distress could lead to greater benefit for some patients, this would come at the cost of treating infants who would experience improvement without CPAP treatment.
Comparing costs for infants cared for with CPAP versus headbox therapy was a secondary outcome for this study; therefore, the results obtained are estimates, taking into account the most up-to-date cost data available. The cost saving of approximately $10000 attained by using CPAP therapy is an average for the 6 centers. No equipment costs were calculated for infants who had a pneumothorax requiring treatment. It is possible that infants with a pneumothorax requiring drainage had a longer length of stay in a NICU, compared with those without a pneumothorax. However, there was no significant difference between the CPAP and headbox groups overall in the median length of stay in a NICU. Transport costs vary considerably according to the mode of transport and the distance traveled. We consider this to be an underestimate of cost savings, because the cost of caring for an infant receiving CPAP therapy (the greatest component of cost estimates) assumed a nurse/patient ratio of 1:2. Actual nurse/patient ratios varied from 1:2 to 1:6 in this trial. Unmeasured in these costs is the impact that a transfer has on the family unit.
The proportion of infants who had a pneumothorax was greater in the CPAP group (9.3% vs 3.4%). A nonsignificant increase was also identified in the Cochrane review, with 19% of the CPAP-treated infants, compared with 8.3% of the headbox-treated infants, developing a pneumothorax (P = .10).11 The higher rates in the Cochrane review might reflect the younger sicker population. It is unlikely that any pneumothoraces were missed in this trial, because only 3 infants did not receive a chest radiograph. We suggest that CPAP treatment may lead to a clinically important increase in pneumothorax. Anecdotally, the pneumothoraces that developed and required drainage in the NTCs were not under tension. We think that the reduction in up-transfer conferred by CPAP therapy outweighs the increase in the rate of pneumothorax.
No difference was detected for any other measure of morbidity or death. We had hypothesized that infants treated with CPAP therapy would get better faster and therefore would spend fewer days in a nursery. This was not found, which might have been because of the very large variation in the number of days spent in the nursery (range: 1.0–67.6 days). Most of this variation is likely to be attributable to factors other than the issue of respiratory distress, including the establishment of oral feeding and the gaining of weight.
Intraventricular hemorrhage, the need for oxygen for >28 days, and death are all uncommon events in this population.22–24 The decision to order a head ultrasound scan was left to the discretion of the doctor caring for the infant, and a scan was ordered for 29% of the infants enrolled. In keeping with clinical practice, head ultrasound scans were statistically significantly more likely to have been ordered for infants of younger gestational age (
2 = 22.9; P < .0001) and those who either experienced treatment failure or were up-transferred, compared with those who did not or were not (39% vs 26%; P < .03). Although the number of intraventricular hemorrhage episodes was higher in the headbox group, none was of clinical significance.
Inclusion and exclusion criteria were designed to identify as early as possible the infants who were most likely to require transfer to a NICU, while excluding infants with transient respiratory distress during adaptation. All centers continued to follow the Australian national guidelines, which recommend transfer of infants in utero at a gestational age of <33 weeks when possible.25 Pediatricians excluded 39 infants who were otherwise eligible on the basis that they were too sick. Exactly why the infants were thought to be too sick is not known. However, the inclusion in this study of infants with a range of final diagnoses, including respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration, pulmonary hypertension, and neonatal encephalopathy, supports the generalizability of using CPAP therapy for most infants with respiratory distress who meet the eligibility criteria of this trial.
All nurseries were located in hospitals that deliver 2000 to 3000 infants per year. During the trial, there were, on average, 22 infants per year who were eligible for CPAP therapy at each SCN. In a nontrial setting, we think it would be difficult for clinical staff members to maintain CPAP skills unless they cared for an average of 1 infant receiving CPAP treatment per month. This study used an underwater bubble form of CPAP delivery, with short nasal prongs as the patient interface. Many centers use different CPAP delivery systems. There are no randomized trials comparing approaches in a SCN environment.
There were 13 up-transfers of infants who had not met failure criteria in the headbox group and 5 in the CPAP group (P = .06). The mean highest recorded FIO2 for these infants was 47% in the headbox group and 44% in the CPAP group. Although the rate of up-transfer without treatment failure was higher in the headbox group, it should be noted that there remained a significantly lower rate of treatment failure alone in the CPAP group.
A posthoc logistic regression analysis was undertaken to identify any possible confounders. The variables examined were birth weight percentile according to gestational age,26 gender, presence/absence of meconium-stained fluid, Apgar score at 1 minute, Apgar score at 5 minutes, resuscitation provided (none/any), treating SCN, and timing of treatment (before/after interim analysis). All yielded a <5% change in the effect size of treatment, and none was considered to be a confounder.
CPAP therapy provides significant benefits to infants with respiratory distress and their families, in large NTCs with appropriate staff training. The optimal time to commence CPAP treatment and the oxygen saturation levels to target for these infants require additional study.
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APPENDIX: MANAGEMENT GUIDELINES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX: MANAGEMENT GUIDELINESREFERENCES |
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Introduction
The bubble CPAP study design was formulated through consensus of the CPAP study committee. This committee included neonatologists from centers that do and do not use CPAP therapy as their primary method of respiratory support and pediatricians from each of the 4 participating centers, with input from the New South Wales newborn emergency transport service. The development of the guidelines was facilitated by a survey of all participating pediatricians regarding current practices and thresholds for transfer; the survey had an 83% response rate. The aim of these guidelines is to ensure adherence to the protocol with safety. The committee thinks that the clinical needs of the infant and the responsible pediatrician's judgment of those needs, including the decision to transfer the infant or not, should have priority at all times. If there is any uncertainty, then discussion should occur.
Uncertainty
It is likely that difficult-to-answer questions will arise during the study. These questions are likely to fall into 3 categories. Questions relating to the study protocol should be addressed to Dr Adam Buckmaster or the study coordinator. Questions relating to the mechanics of CPAP treatment should be addressed to the supporting NICU. Questions relating to clinical management or transfer should be addressed to the newborn emergency transport service and/or the receiving NICU.
Oxygen
All infants with respiratory distress who are able to breathe easily without assistance should initially be treated with 30% headbox oxygen therapy. The CPAP study committee thinks that this is a safe, reasonable, starting point for any newborn with respiratory distress. The FIO2 may be increased rapidly or weaned, with the aim of keeping the oxygen saturation between 94% and 96%. There is no evidence that it is effective to use 100% oxygen to treat presumed pulmonary hypertension in infants born with meconium-stained fluid; 100% oxygen is undoubtedly toxic.
Consent
Consent may be obtained before an infant becomes eligible, to enable more-rapid commencement of CPAP therapy should the infant become eligible and be so allocated. Randomization cannot occur until the infant is eligible. It is recommended that a pediatric registrar or consultant obtain consent, with the SCN nurse caring for the infant being present.
Eligibility
Infants must meet all of the following criteria to be eligible for random assignment: age of 30 minutes to 24 hours, gestational age of 31 weeks (32 weeks at Blacktown District Hospital), weight of 1200 g, 5-minute Apgar score of 4, 1 sign of respiratory distress (nasal flare, tachypnea, grunt, or recession), and requirement for >30% oxygen to keep oxygen saturation values at 94% for >30 minutes.
Twins/Multiple Births
Once an infant from a multiple birth becomes eligible and is assigned randomly, then any other infants from the same set of multiple births cannot be eligible for the trial even if they develop respiratory distress.
Meconium
Being born with meconium-stained fluid is not an exclusion criterion. Infants with "gasping respirations" or respiratory rates that are low should be assisted in ways other than CPAP therapy and therefore are not appropriate for enrollment in the study. Infants who are eligible but not assigned randomly, because of either parental refusal or consultant's choice, must be recorded, with the reason, for later analysis.
Oximetry
The protocol requires oxygen saturation to be targeted between 94% and 96%. Maintaining oxygen saturation within the narrow range prescribed for the study is considered by the CPAP study committee to be both reasonable and safe. The level is slightly higher than in some NICUs. The same brand of oximeter (within each hospital) must be used for all infants assigned randomly in the study, whether in the headbox group or in the CPAP group. Significant differences exist between brands in oxygen saturation readings, and this must not be allowed to contaminate the results.
Chest Radiographs
Where possible, a chest radiograph should be obtained for all infants as soon as they become eligible for the trial. Obtaining a chest radiograph should not unduly delay the implementation of CPAP therapy; CPAP therapy should commence within 30 minutes from the time the infant becomes eligible. A chest radiograph should also be obtained for infants whose conditions are deteriorating despite treatment and those who are being transferred. These recommendations are in accordance with usual clinical practice. Additional chest radiographs may be arranged as clinically indicated (eg, uncertainty regarding the working diagnosis or regarding a clinical change).
Blood Gas Analyses
All infants sick enough to be eligible for the study should have a blood gas analysis performed either before randomization or between 1 and 2 hours after randomization (infants assigned to CPAP therapy need time to adjust to the new treatment; repeat procedures, such as blood gas analyses and radiographs, and cannulation should be avoided in the first hour, if possible). If the pH is <7.25 or the CO2 level is >60 mm Hg in any blood gas analysis, then a second measurement should occur between 1 and 4 hours after the first, as indicated clinically. Additional blood gas samples may be collected as indicated clinically (eg, deterioration or continuing high oxygen requirements). The same method for collection of blood gas samples (capillary, venous, or arterial) should be used consistently by each hospital for both the control and intervention groups. It should be remembered that the mechanics of the immature ventilatory system of neonates promote an early increase in CO2 levels. Therefore, an increase in CO2 levels does not necessarily indicate that the infant is tiring. The blood gas results need to be interpreted in the context of the infant's work of breathing. Assessment of the trend through repeated examinations by the same experienced observer gives the best information about the infant's progress and margins of safety. If there is any uncertainty, then discussion should occur.
Infants Assigned to CPAP Therapy
It is expected that all infants assigned to receive CPAP therapy commence treatment within 30 minutes after becoming eligible. Delays may reduce any potential benefit of CPAP therapy. Once CPAP therapy has commenced, all other procedures should be avoided, where possible, to enable the infant to adjust and to settle. Failure to improve or deterioration with CPAP therapy is most commonly caused by a problem with CPAP delivery and may be sudden. Common causes to be excluded or treated include blockage of nares or prongs, inappropriate size of prongs, circuit failure, and open mouth. Other causes of deterioration to consider are a pneumothorax or air leak and the natural course of the underlying disease process.
Pneumothorax
A pneumothorax is the most likely serious complication of bubble CPAP treatment. A trivial pneumothorax without symptoms does not automatically require drainage and does not preclude the use of CPAP therapy. Each unit must have guidelines and procedures in place for management of acute pneumothorax. The decision to drain or not should be based on the clinical needs of the patient. There is no evidence that it is effective to use 100% oxygen to promote more-rapid resolution of a pneumothorax. If there is uncertainty, then discussion should occur.
Treatment Failure and Transfer
For the purposes of the study, treatment is considered to have failed if any of the following criteria are met: for headbox oxygen treatment only, requirement for 60% oxygen to maintain oxygen saturation at 94% for 1 hour (75% of pediatricians would definitely transfer an infant requiring >60% oxygen); for CPAP therapy only, requirement for 50% oxygen to maintain oxygen saturation at 94% for 1 hour (agreed on by representatives of NICUs that use CPAP); for both groups, CO2 levels of >60 mm Hg in 2 successive blood gas analyses 1 hour apart (75% of pediatricians would definitely transfer an infant with a CO2 level of >60 mm Hg); for both groups, pH levels of <7.25 in 2 successive blood gas analyses 1 hour apart (75% of participating pediatricians would definitely transfer an infant with a pH of <7.25). It is recommended that transfer occur or that discussion with the newborn emergency transport service or the preferred receiving NICU take place. Transfer may take place at any time before these criteria are met, after discussion between the pediatrician and the newborn emergency transport service and/or the potential receiving hospital. The reason for transfer must be noted if transfer occurs before the criteria are met.
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ACKNOWLEDGMENTS |
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This trial was funded through financial grants from the Australian National Health and Medical Research Council and the Financial Markets, Bow Tie Foundation for Children.
We thank all of the following investigators, research nurses, and hospitals, without whose hard work and dedication the trial would not have been possible. The following participated in the trial: enrolling centers (listed according to number of infants they enrolled): Blacktown District Hospital, Blacktown, New South Wales: D. Green, M. Murray; Wollongong District Hospital, Wollongong, New South Wales: P. Kristidis, S. Lees, B. Van Klooster; Gold Coast Hospital, The Gold Coast, Queensland: E. Chappell, G. Harte, S. Moloney, C. Van den Berg, M. Van Drimmelen; Gosford District Hospital, New South Wales: M. Biddle, A. Buckmaster, K. Field; St George Hospital, Kogarah, New South Wales: S. Bowdler, D. Buckle, B. Fonseca, P. Gallagher, T. Grattan-Smith, S. Grove, A. Hurst, M. Ninic; Campbelltown District Hospital: R. Chin, M. Cooke, L. Mitchell, N. Young; Safety Committee: E. Elliott, R. Henry, K. Spence; input to Steering Committee: all of the above; New South Wales Pregnancy and Newborn Services Network, University of Sydney, Camperdown, New South Wales: G. Arnolda, B. Bajuk, J. Foster, D. Henderson-Smart, J. Kent Biggs, Y. McCann, K. Smith; John Hunter Hospital, Newcastle, New South Wales: S. Graham, J. Parsons, C. Wake, I. Wright; Newborn and Pediatric Emergency Transport Service, Westmead, New South Wales: A. Berry, J. Dawson, T. Grattan-Smith, J. Nash; Westmead Perinatal Unit, Westmead, New South Wales: W. Tarno-Mordi; Liverpool Neonatal Unit, Liverpool, New South Wales: R. Guaran; assistance with posthoc analysis: J. Simpson.
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FOOTNOTES |
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Accepted Apr 13, 2007.
Address correspondence to Adam G. Buckmaster, MBBS, FRACP, Northern Sydney Central Coast Area Health Service, Gosford Hospital, PO Box 361, Gosford, NSW, 2250 Australia. E-mail: abuckmaster{at}nsccahs.health.nsw.gov.au
The authors have indicated they have no financial relationships relevant to this article to disclose.
The funding sources played no role in study design, data collection, data analysis, writing of the report, or the decision to submit the manuscript for publication.
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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