NICU Bedside Caregivers Sustain Process Improvement and Decrease Incidence of Bronchopulmonary Dysplasia in Infants < 30 Weeks Gestation

Discussion

In this study, implementation of a respiratory bundle managed primarily by nurses and respiratory therapists was successful in implementing less invasive respiratory support and decreasing oxygen exposure in a consistent manner among VLBW infants at a single institution. However, this study failed to show sustained improvement in the incidence of BPD despite sustained process change. Significant clinical improvements have been sustained through 4 y post-implementation such as the significant decrease in ventilator days and increase in CPAP days. Additionally, an increase in the percentage of infants receiving surfactant in the first postnatal hour and infants receiving caffeine therapy demonstrates continued utilization of these specific clinical interventions in the bundle.

A decreased BPD rate was appreciated in the first 2 y after implementation at our institution. Following logistic regression analysis controlling for the significant confounders including gender, gestational age, birthweight, rate of prenatal care, antenatal steroids, postnatal steroids, and presence of PDA, this significant decrease persisted. However, a nonsignificant, yet marked increase in the rate of BPD was noted in T4 when compared with T3. Additionally, when comparing survival without BPD at discharge by time period, a statistically significant increase was noted 2 y post-implementation that was not sustained. This raises concern that, despite a persistent decrease in ventilator days, an increase in CPAP, an increase in prophylactic surfactant delivery, and an increase in caffeine therapy, these evidence-based clinical improvements are not associated with improvement in long-term respiratory outcomes.

A unique characteristic of our intervention was reliance predominantly upon the bedside caregivers for implementation and maintenance. Only one other pediatric study has evaluated bedside caregiver-dependent quality improvements in respiratory care. Hermeto et al³⁹ reported the implementation of a respiratory therapist-driven ventilator protocol that was associated with shortened time to first extubation attempt, increased rate of successful extubation, and decreased duration under mechanical ventilation in infants < 1,250 g at birth. There was also a nonsignificant, yet appreciable decrease in rate of infants requiring oxygen at 28 d. The incidence of BPD, or oxygen requirement at 36 wk PMA, was not statistically different between groups. The study was not powered sufficiently to examine these respiratory outcomes. There are few pediatric articles describing pediatric ventilator protocols and outcomes.^40,41 This is in contrast to the adult literature, in which several randomized trials and prospective case series involving protocols directed by nursing, respiratory therapy, and computers have been associated with decreased times on mechanical ventilation and other improved outcomes.^42–47

A 2004 study by Aly et al⁴⁸ demonstrated sustainable improvements in the rates of BPD and similar outcome variables such as a decrease in ventilator days and an increase in CPAP use after implementation of an early nasal CPAP management strategy. Other studies have evaluated respiratory care interventions but without a measurement of sustainability. Birenbaum and colleagues⁵ demonstrated successful process outcomes such as increased use of the T-piece resuscitator in the delivery room, increased use of nasal CPAP in the delivery room, and decreased time on mechanical ventilation at a single institution. They found a reduction in the incidence of BPD from 46.5% in 2002 to 20.5% in 2005, with an overall relative risk reduction of 55.8% following implementation of quality improvements. However, they did not evaluate the ability to sustain these clinical processes or results.

Likewise, the NIC/Q Breathsavers group in 2002 noted improvements in process outcomes including decreased time on mechanical ventilation, time to initial surfactant administration, and increased CPAP use following identification and implementation of 13 potentially better practices among 18 participating centers. There was also a noted 27% overall reduction in the incidence of BPD over a 2-y period following implementation of clinical modifications.^4,49 However, the participating centers aimed at reducing BPD rates demonstrated markedly varying results. Some NICUs with low baseline rates of BPD demonstrated paradoxical increases in BPD rates.⁶ Payne et al⁴ described the possibility of the Hawthorne effect, or the improvement in performance that is seen when performance receives extra scrutiny, that may have contributed to improved outcomes in their study. Participants in these collaboratives are also self-selected and highly motivated individuals, and these factors may well have contributed to the improved rates of BPD initially observed with the Breathsavers group, as well as with our study.⁶ It is a possibility that our bedside caregivers experienced “bundle fatigue” with time, which may have contributed to the increase in BPD rates observed in T4 in our study.

Another monitor of respiratory outcomes is survival without BPD, or BPD-free survival. In a cluster-randomized trial that involved 17 centers of the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, benchmarking and multimodal quality improvement were successful in changing practice such as reducing oxygen exposure and mechanical ventilation duration, but did not reduce the rate of survival free of BPD.⁵⁰ Similarly, Horbar et al⁵¹ did not demonstrate a significant decrease in the combined outcome of death or O₂ supplementation at 36 wk despite significant measureable process change in the 4 participating NICUs. These findings are consistent with the results of our observational study that, despite successful, sustained implementation of evidence-based quality improvements in respiratory care emphasizing noninvasive respiratory support, long-term outcomes such as BPD-free survival may not sustain positive change.

What could account for the discrepancy of improved respiratory care with less oxygen need at 28 d but with persistence in prevalence of BPD? BPD is known to be a complex, multifactorial disease process, illustrated by the finding that some VLBW infants demonstrate little to no initial lung disease, but subsequently develop BPD.⁵² Barotrauma and volutrauma by mechanical ventilation, combined with atelectotrauma, and exposure to oxygen toxicity contribute to inflammatory reactions that persist past the immediate neonatal period and contribute to the development of BPD.^53–56

At the time of this study, there was only one T-piece resuscitator available in the NICU for bedside resuscitation or unintended extubation. This was often reserved for the most immature or critically-ill infants, or infants with air leak. Otherwise, a neonatal manual resuscitation bag would have been utilized in those clinical situations. There were also no F_IO2 blenders at bedside at the time of the study. T-piece resuscitators and blended F_IO2 were present and utilized for all VLBW deliveries in the delivery room. One could speculate that respiratory care administered at the bedside with bag-valve-mask and oxygen exposure may be a significant contributor to the development of BPD. As animal studies have demonstrated, just 6 large tidal volume breaths had potential to cause severe preterm lamb lung injury.⁵⁷ The subsequent inflammatory response that ensues may contribute to a protracted course of lung injury. Unfortunately there was no standardized collection of data surrounding unintended extubations or number of positive-pressure events at bedside in the NICU at the time of the study. The lack of this pertinent clinical information is a limitation to our study, given the retrospective study design.

There has also been emerging evidence to suggest that initiation of CPAP for extremely preterm infants is an acceptable alternative to prophylactic surfactant administration. The SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network randomized > 1,300 extremely low birthweight neonates to either CPAP or intubation, prophylactic surfactant within 1 h of life followed by a brief period of ventilation. The primary outcome of death or BPD was no different between the groups. However, infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for BPD (P < .001), required fewer days of mechanical ventilation (P = .03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P = .01). The rates of other adverse neonatal outcomes did not differ significantly between the 2 groups.⁵⁸ The design of our bundle incorporates a brief period of mechanical ventilation and a weaning protocol similar to the prophylactic surfactant arm of this study. Any positive-pressure ventilation delivered to preterm infants may contribute to a cascade of inflammatory reactions that may subsequently contribute to the development of BPD.⁵⁷ Given the SUPPORT trial outcome, early use of noninvasive support such as CPAP without intubation and ventilation may have also contributed to the sustained success documented by Aly et al⁴⁸ in decreasing the incidence of BPD at their institution.

Another reason for the discrepancy between improved respiratory techniques and sustained outcome may be that definitions of BPD lack a rigorous, consistent approach to integrating oxygen delivery into the diagnosis. Walsh and colleagues⁵⁹ demonstrated that the development and implementation of a rigorous physiologic definition of BPD that included a room air challenge for infants receiving < 30% effective oxygen resulted in a mean reduction of 10% in rates of BPD. At the time this study was conducted, no uniform guidelines for nasal cannula weaning or for a room air challenge at 36 wk PMA were in place at our institution. Additionally, some clinicians implement oxygen therapy for preterm infants with poor oral feeding technique or apnea and desaturation events during feeds. Infants may be discharged to home on oxygen solely to be utilized during feeds and are misdiagnosed as having BPD without meeting true physiologic criteria. Despite little evidence to support this practice, it continues to occur and may contribute to the discrepancy noted between O₂ requirement at 28 d and 36 wk PMA at this institution.

An unexpected outcome in our study was a nonsignificant, yet marked increase in the use of postnatal steroids during the study period. However, despite the rise in postnatal steroid use, the rate of BPD continued to increase from T3 to T4 after controlling for this variable. Since the American Academy of Pediatrics policy statement in 2002 stating that routine dexamethasone therapy could not be recommended without further study and long-term follow-up, postnatal steroid use in preterm infants has decreased.⁶⁰ There have been 2 randomized controlled trials published since the 2002 policy statement demonstrating increased successful extubation with later, low-dose dexamethasone compared with control. Neither study was powered to evaluate the effect of the treatment on survival without BPD.^61,62 The increase in steroid use at our institution noted during this study may be in part to the adoption of practice to administer later, low-dose dexamethasone to facilitate extubation in chronically ventilated infants. This has been noted as a potential confounder as well as limitation in this retrospective study design.

The increased rate of PDA observed across the study period was also an unexpected outcome. The increase in rate of PDA may be explained by a few clinical factors. There was practice variation among clinicians regarding PDA management. Data regarding management strategies were not collected, and this is a limitation to the study. The practice to give prophylactic indomethacin to neonates < 1,000 g at birth was routine among clinicians early in the study period. However, this practice was discontinued in T4. This time point was not collected and not accounted for in the statistical analysis. There was also practice variation among obstetricians regarding agents used for tocolysis of preterm labor. Indomethacin was frequently used as a tocolytic agent during this time period and could also contribute to the increased rates of PDA if fewer women received prenatal care, and therefore indomethacin exposure. The data regarding use of indomethacin for tocolysis among the obstetricians were not collected and accounted for in the statistical analysis and are therefore another limitation to the study.

There are few data supporting the role of PDA in the development of BPD. To date, there is only one randomized controlled trial, which was performed in the 1970s, that has examined the pulmonary effects of prolonged exposure to PDA in extremely premature infants requiring mechanical ventilation. The investigators compared the effects of ligating the PDA versus allowing PDA to persist and found that ligation decreased the need for prolonged mechanical ventilation.⁶³ Studies have suggested that the mean airway pressure and F_IO2 needed to overcome PDA-induced changes in pulmonary compliance may contribute to the development of BPD; however, there is little evidence from controlled clinical trials.^63–65 An additional limitation of the study is the lack of data such as mean airway pressures, mean CPAP levels, and F_IO2 requirements. In addition, because it was a before-and-after study, the possibility exists that other unrecognized changes were taking place concurrently with the study.