Hyperinflation and its Association with Successful Transition to Home Ventilator Devices in Infants with Chronic Respiratory Failure and Severe Bronchopulmonary Dysplasia

doi:10.21203/rs.3.rs-1739130/v1

Download PDF

Article

Hyperinflation and its Association with Successful Transition to Home Ventilator Devices in Infants with Chronic Respiratory Failure and Severe Bronchopulmonary Dysplasia

https://doi.org/10.21203/rs.3.rs-1739130/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 13 Dec, 2022

Read the published version in Journal of Perinatology →

You are reading this latest preprint version

Objective

To estimate the association between lung hyperinflation and the time to successful transition to outpatient ventilators in infants with sBPD and chronic respiratory failure.

Design/Methods:

Infants with sBPD < 32 weeks’ gestation who received tracheostomies were identified. Hyperinflation was the main exposure. Time from tracheostomy to successful transition to the outpatient device was the main outcome. Kaplan-Meier and multivariable Cox proportional hazards were used to estimate the relationships between hyperinflation and the main outcome.

Results

Sixty-two infants were included; 26 (42%) were hyperinflated. Eleven died before transition, and 51 successfully transitioned. Hyperinflation was associated with both mortality (31% vs 8.3%, p = 0.02) and an increased duration (72 vs. 56 days) to successful transition (hazard ratio (HR) = 0.38, 95% CI: 0.19, 0.76, p = 0.006). Growth velocity was similar after tracheostomy placement.

Conclusions

In infants with chronic respiratory failure and sBPD < 32 weeks’ gestation, hyperinflation is related to mortality and inpatient morbidities.

Severe bronchopulmonary dysplasia (sBPD) affects 20% of preterm infants < 32 weeks’ gestation(1, 2), and confers risks of mortality, prolonged hospital stays, cardiopulmonary morbidities, and neurodevelopmental impairment in early childhood(3). Approximately 5% of infants with sBPD develop chronic respiratory failure and require chronic mechanical ventilation via tracheostomy. Together, these therapies permit maintaining physiologic stability to follow a trajectory focusing on enhancing growth and physical, cognitive, and social development(4). The ability to transition to an outpatient, mechanical ventilator (MV) in these infants is a pre-requisite to facilitate safe discharge from the hospital (5, 6). However, the timing and success, as well as patient-level predictors of successful transition to outpatient MVs, may be uncertain in a subset of these infants.

Chronic respiratory failure with sBPD is often characterized by combinations of heterogeneous lung development, architecture, and dysfunction with cystic and hyperinflated airspaces, shifting atelectasis, and airway malacia. (7, 8). With these pathologies, lung hyperinflation may impede flow-triggering on MVs. Though the mechanisms are not clearly delineated, impaired flow-triggering with hyperinflation may lead to inefficient, if not paradoxical, diaphragmatic excursion and asynchronous air-flows with MVs(9). Despite adjusting the sensitivities of MV’s flow-triggering, we have noticed that transitions to outpatient ventilators can frequently be unsuccessful among those infants with significant asynchrony, and many of these infants are also hyperinflated on their chest radiograph (CXR) (10). In the current project, we seek to identify and understand whether hyperinflation is related to a delayed transition to outpatient MVs based on the presumed mechanism outlined. Understanding this relationship would lead to more accurate parental counseling and perhaps more targeted preventive and management strategies and that may improve both hyperinflation and perhaps alter the course of affected infants after tracheostomy placement.

We hypothesize that infants with sBPD and hyperinflation have delayed transition to outpatient MVs after tracheostomy. Our main objective is to estimate the association between time to successful transition to outpatient MVs and hyperinflation among patients with sBPD < 32 weeks’ gestation and chronic respiratory failure.

Using our center’s data in the Children’s Hospital Neonatal Database, we reviewed medical records of infants with sBPD < 32 weeks’ gestation that underwent a tracheostomy between 2010 and 2018 at our center. SBPD was defined as infants receiving > 2 L/min via nasal canula or positive-pressure ventilation at 36 weeks’ post-menstrual age (PMA) as prior studied(11, 12). We excluded infants who received a tracheostomy prior to transfer to our institution, were born > 32 weeks’ gestation, had significant congenital anomalies, or who recovered sufficiently to avoid mechanical ventilation post-tracheostomy.

The primary outcome was the time to successful transition to an outpatient MV, and this was defined as stability for 7 consecutive days after transition from the inpatient MV device. Reversion back to an inpatient MV prior to this time was considered unsuccessful. However minor adjustments in settings (rate, PEEP) were not characterized as failure. Almost exclusively, we transitioned patients to an LTV™ (Vyaire Medical, Inc™; Chicago, IL) for their outpatient care. In general, stability was defined as acceptable gas exchange (P_vCO2 ~ 50 mmHg, F_iO₂ < 0.35); respiratory rate ( < ~ 60/min while awake); acceptable respiratory effort (minimal dyspnea during sleep); absence of intravenous sedative or analgesic medications; peak inspiratory pressures < 35 cm H₂0, positive end expiratory pressure < 12 cm H₂0; and inspiratory time of 0.7 seconds. Lack of success was coded when patient dyspnea, distress, or impairment in gas exchange were noted. Though some of these are subjective criteria, these have been consistently established in our clinical practice.

The primary exposure was collected from the portable CXRs most adjacent to the time tracheostomies were placed: the presence of hyperinflation was defined as 10 or more posterior ribs expanded above the diaphragm on the right side. The CXR was generally reviewed by two neonatal clinicians (authors ML, RC, MR) to minimize variability. Radiologists’ written interpretations were considered though sometimes comments on hyperinflation were missing as they had been written in prior interpretations of radiographs. Adjudication was made by consensus between these radiologists’ and clinicians’ interpretations.

Maternal characteristics and infant variables related to prematurity- or BPD-associated morbidities were ascertained through medical record review. Also, because affected infants may develop pulmonary hypertension concurrent with their respiratory failure, we quantified whether infants had right ventricular dilation (yes/no) based on echocardiography done prior to their tracheostomy insertion. Stratified by hyperinflation (≥ 10 ribs), we observed and calculated differences in these characteristics using bivariate analyses, and correspondingly, student t-test, Chi-square, or nonparametric testing, as appropriate.

To observe the timing of transition, we created Kaplan-Meier curves also stratified by hyperinflation. Then, multivariable Cox proportional hazards models were created to determine whether hyperinflation was independently associated with the main outcome. Candidate variables were those hypothesized to influence this duration that were present and known at the time of tracheostomy, and those that were significantly associated with the primary outcome in bivariable analyses (p < 0.2) were considered. Backward selection was used, and variables were retained if they were significantly associated with the main outcome and the association between hyperinflation and the primary outcome changed by 20%.

Secondary outcomes included growth velocity after tracheostomy. Analyses were performed using STATA v14 (College Station, TX), and institutional review board oversight was obtained prior to medical record chart review (2011–2019) and prior to establishing or accessing CHND (2009–13982).

Eighty-one patients with tracheostomy and a diagnosis of sBPD were identified. After excluding infants born > 32 weeks’ gestation, those who did not require home MVs or received tracheostomy prior to transfer and those with significant congenital anomalies, 62 patients and their data were analyzed (Fig. 1).

Of these 62 infants, 26 (42%) were noted to be hyperinflated by CXR (Table 1). Infants with hyperinflation were less likely to be multiple gestation. Otherwise, no other significant differences were observed between infants with and without hyperinflation.

Table 1

Characteristics of infants stratified by hyperinflation
	No hyperinflation (≤ 9 ribs)	Hyperinflation (≥ 10 ribs)	p-value
N (%)	36 (58%)	26 (42%)
Mean gestational age (SD), weeks	25.8 (2.3)	25.5 (1.8)	0.6
Female sex, n (%)	17 (47)	7 (27)	0.11
Median birth weight (g)	702 (565, 965)	685 (520, 760)	0.22
Maternal race/ethnicity, n (%)			0.72
White	11 (30)	4 (15)
Black	13 (36)	11 (42)
Other	12 (33)	11 (42)
*Antenatal steroids (Full or partial), n (%)	30 (82)	20 (78)	0.31
*Chorioamnionitis, n (%)	5 (14)	5 (19)	0.3
Multiple gestation, n (%)	8 (22)	1 (4)	0.043
Small for Gestational Age (Olsen 2010)	7 (19)	10 (38)	0.098
Intraventricular hemorrhage, n (%)	13 (36)	11 (42)	0.62
Culture-positive blood stream infection	7 (19)	7 (27)	0.487
Atrial septal defect	11 (31)	4 (15)	0.169
Ventricular septal defect	2 (6)	4 (15)	0.169
Right ventricular dilation prior to tracheostomy	22 (58)	13 (42)	0.384
Abdominal surgery, n (%)	11 (31)	5 (19)	0.32
Weight at time of tracheostomy (1 missing weight in hyperinflated patients), kg	5.24 (3.95, 6.15)	5.0 (3.7, 6.2)	0.78
PMA at time of tracheostomy (weeks)	50.6 (45.6, 57.2)	51.8 (47.4, 60.3)	0.40
* 6 and 3 (hyperinflated) are missing for antenatal steroids; 5 and 2 (hyperinflated) are missing from their respective group for chorioamnionitis

In unadjusted analyses, hyperinflation was associated with a 30% increased duration of time to successful transition from a hospital to home ventilator (72 vs. 56 d; HR = 0.38, 95% CI 0.19-0.0.76, p = 0.006) (Fig. 2). This association persisted in multivariable analyses after controlling for gestational age and right ventricle dilation (Table 2). Specifically, hyperinflation was independently associated with an increased time to transition (HR = 0.30; 95% CI 0.15–0.62, p < 0.001).

Table 2

Multivariable Cox Proportional hazards analyses
	HR	95% CI		P
Hyperinflation	0.30	0.15	0.62	0.001
RV Dilation prior to tracheostomy	0.51	0.27	0.95	0.034
Gestational age, sex, small for gestational age, birthweight, maternal race/ethnicity were not associated with the main outcome

Secondary outcomes demonstrated that infants with hyperinflation had a higher risk of mortality after tracheostomy placement without conversion to LTV (31% vs 8.3%, p = 0.02). Length of NICU stay was significantly longer in infants who had observed hyperinflation (125 vs 83 days, p = 0.018), however, weight-gain velocity after tracheostomy was similar (26.8 vs 30 grams/day, p = 0.31).

In our population of preterm infants with sBPD and chronic respiratory failure, radiographic lung hyperinflation at the time of tracheostomy was associated with a longer time to transition to an outpatient ventilator. This finding was persistent after adjusting for a marker of pulmonary hypertension (right ventricle dilation) and was unaffected when including traditional markers of confounding variables (Table 1). Furthermore, affected infants with hyperinflation had an increased risk of mortality post-tracheostomy and longer NICU length of stay.

Hyperinflation can be a marker of sBPD given the heterogeneous lung disease through the lung parenchyma(13). It may reflect effects of the disease interacting with the type, mode, and/or duration of ventilation prior to tracheostomy. Hyperinflation may also reflect illness severity among infants with sBPD and chronic respiratory failure. Regardless, these results call for the need of evidence- and/or pathophysiologic-based strategies and interventions to prevent hyperinflation earlier during preterm infants’ hospitalizations. In addition, given our observations that hyperinflation frequently co-exists with patient-ventilator asynchrony, these results call for a need to understand the relationship between these two and, if verified, develop and utilize alternative triggering of MVs used for affected infants. Finally, these findings may assist clinicians in setting parental expectations for the trajectory of hospitalization, risk of mortality, and process of transitioning to achieve medical stability after tracheostomies are placed among infants with sBPD and chronic respiratory failure.

Air trapping and intrinsic positive end expiratory pressure (PEEP) are common in sBPD (14, 15), and prior studies have demonstrated links between hyperinflation, intrinsic PEEP and ventilator asynchronies (8, 16, 17). We have observed similar findings in our clinical practice. These asynchronies can lead to ventilator-induced lung injury and can contribute to further ventilator-induced diaphragmatic dysfunction(18). Furthermore, asynchrony has a known association with increased risk for mortality(19). Detecting asynchrony is often difficult, requiring direct observations of the patient’s respiratory pattern and the timing of the MV’s delivery of each breath (8). Asynchrony may be intermittent and related to patients’ sleep-wake cycles and other clinical states (e.g., inadequate sedation, post-operative pain)(19). Sometimes, “BPD spells” and asynchrony co-exist which appear to contribute to cardiopulmonary instability. Thus, the burdens of MV asynchrony are important on these infants. Though we cannot establish a causal link to whether hyperinflation causes asynchrony, our clinical observations suggest that hyperinflation and its ramifications deserve further exploration.

CXRs demonstrating hyperinflation can alert a clinician to the increased risk for impaired ventilator synchrony and allow earlier modifications in management strategies. Identifying effective strategies to prevent, treat, or mitigate concurrent co-morbidities (e.g., airway malacia) require rigorous clinical trials to reduce burdens of chronic respiratory failure on infants with sBPD.

Our results show that mortality risks are greater among those who exhibited radiographic hyperinflation, which underscores the necessity to understand more about its pathophysiology so preventive strategies can be undertaken, if possible. Our findings may help to explain why, at the moment of transition, ventilator settings may need substantial adjustment to more chronic settings based on the underlying pathophysiologic findings (e.g., longer time constants, larger dead space, ventilation-perfusion mismatching). Given the result in this study that more patients with hyperinflation died than those without, earlier adjustment of support to mitigate pathologic air trapping may be helpful, though further study and examinations are clearly needed.

Delaying transition to outpatient MV most clearly contributes to longer hospitalization. However, other factors are still critical to a successful, safe discharge. In addition to respiratory stability, somatic growth, and minimizing withdrawal symptoms from polypharmacy regimens, obtaining home nursing care, parental education, and administrative support systems in the outpatient settings are complex to attain and secure(20). Our results do not address these necessary components to successful discharge, and thus, further systems and improvements are needed in addition to mitigating hyperinflation to make material decreases in lengths of hospitalizations for these medically complex infants.

This study has important limitations. Hyperinflation was defined subjectively and arbitrarily, and CXR ascertainment during exhalation or inhalation was not controlled. Second, these results are subject to confounding by indication, namely that the CXR appearance may have altered the management of these infants which then changed the association between hyperinflation and the time-to-successful transition to the outpatient MV. Third, the measurement of hyperinflation is a surrogate marker for patient-MV asynchrony. Some hyperinflated infants may not have exhibited MV asynchrony, and conversely, other infants without hyperinflation struggled with synchronizing with an MV. Still, our clinical experience and observation suggested that hyperinflation was tightly associated with asynchrony. Lastly, our results may not be generalizable to others’ practice/hospitals or other MVs (e.g., neurally-activated triggering) where hyperinflation may be less impactful as inspiratory flow is not necessary to trigger a breath.

Understanding the time course, and its determinants, from tracheostomy through achieving medical stability on the outpatient MV has value in infants with chronic respiratory failure and sBPD. Affected infants and families have typically been hospitalized for months already, and a clinical management path to achieve safe, effective outpatient home ventilation can be achieved with multiple preparatory investments. This study describes some of these patterns as an inpatient as we support these children toward having developmental gains that are challenging, and rarely achieved in the NICU hospital setting.

Conflicts of Interest:

Dr. Murthy is a Board member of Children’s Hospitals Neonatal Consortium, a 501c3 organization that developed and maintained a database that was used to identify database records of infants for this project.

Financial Disclosures: none

Padula MA, Grover TR, Brozanski B, Zaniletti I, Nelin LD, Asselin JM, et al. Therapeutic interventions and short-term outcomes for infants with severe bronchopulmonary dysplasia born at < 32 weeks' gestation. J Perinatol. 2013;33(11):877–81.
Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, et al. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005;116(6):1353–60.
Cammack B, Noel-MacDonnell J, Cuna A, Manimtim W. Impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia. J Perinatol. 2020;40(2):299–305.
Luo J, Shepard S, Nilan K, Wood A, Monk HM, Jensen EA, et al. Improved growth and developmental activity post tracheostomy in preterm infants with severe BPD. Pediatr Pulmonol. 2018;53(9):1237–44.
Willis LD, Lowe G, Pearce P, Spray BJ, Willis R, Scott A, et al. Transition From an ICU Ventilator to a Portable Home Ventilator in Children. Respir Care. 2020;65(12):1791–9.
Yallapragada S, Savani RC, Munoz-Blanco S, Lagatta JM, Truog WE, Porta NFM, et al. Qualitative indications for tracheostomy and chronic mechanical ventilation in patients with severe bronchopulmonary dysplasia. J Perinatol. 2021;41(11):2651–7.
Abman SH, Collaco JM, Shepherd EG, Keszler M, Cuevas-Guaman M, Welty SE, et al. Interdisciplinary Care of Children with Severe Bronchopulmonary Dysplasia. J Pediatr. 2017;181:12–28 e1.
Napolitano N, Jalal K, McDonough JM, Monk HM, Zhang H, Jensen E, et al. Identifying and treating intrinsic PEEP in infants with severe bronchopulmonary dysplasia. Pediatr Pulmonol. 2019;54(7):1045–51.
Esperanza JA, Sarlabous L, de Haro C, Magrans R, Lopez-Aguilar J, Blanch L. Monitoring Asynchrony During Invasive Mechanical Ventilation. Respir Care. 2020;65(6):847–69.
Baker CD, Martin S, Thrasher J, Moore HM, Baker J, Abman SH, et al. A Standardized Discharge Process Decreases Length of Stay for Ventilator-Dependent Children. Pediatrics. 2016;137(4).
Vyas-Read S, Logan JW, Cuna AC, Machry J, Leeman KT, Rose RS, et al. A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children's Hospitals Neonatal Consortium Severe BPD Group. J Perinatol. 2021.
Lagatta J, Murthy K, Zaniletti I, Bourque S, Engle W, Rose R, et al. Home Oxygen Use and 1-Year Readmission among Infants Born Preterm with Bronchopulmonary Dysplasia Discharged from Children's Hospital Neonatal Intensive Care Units. J Pediatr. 2020;220:40–8 e5.
Polin RA, Abman SH, Rowitch DH, Benitz WE. Fetal and neonatal physiology. 6. ed. Philadelphia: Elsevier, Inc; 2022. p1710–1722.
Zhang H FW. Assisted Ventilation of the Neonate: An Evidence- Based Approach to Newborn Respiratory Care. 6th ed. Philadelphia, PA: Elsevier; 2016. 380 – 90 p.
Higano NS, Ruoss JL, Woods JC. Modern pulmonary imaging of bronchopulmonary dysplasia. J Perinatol. 2021;41(4):707–17.
Gibbs K, Jensen EA, Alexiou S, Munson D, Zhang H. Ventilation Strategies in Severe Bronchopulmonary Dysplasia. Neoreviews. 2020;21(4):e226-e37.
Sousa MLA, Magrans R, Hayashi FK, Blanch L, Kacmarek RM, Ferreira JC. Predictors of asynchronies during assisted ventilation and its impact on clinical outcomes: The EPISYNC cohort study. J Crit Care. 2020;57:30–5.
Lonero M DNMPM, 2019;2:50. Features and management of asynchronies in children. Pediatr Med. 2019;2.
Blanch L, Villagra A, Sales B, Montanya J, Lucangelo U, Lujan M, et al. Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med. 2015;41(4):633–41.
Sobotka SA, Foster C, Lynch E, Hird-McCorry L, Goodman DM. Attributable Delay of Discharge for Children with Long-Term Mechanical Ventilation. J Pediatr. 2019;212:166–71.

There is NO conflict of interest to disclose.

Download PDF

Journal Publication

published 13 Dec, 2022

Read the published version in Journal of Perinatology →

Editorial decision: revise
11 Jul, 2022
Review #2 received at journal
04 Jul, 2022
Review #1 received at journal
22 Jun, 2022
Reviewer #2 agreed at journal
20 Jun, 2022
Reviewer #1 agreed at journal
13 Jun, 2022
Reviewers invited by journal
13 Jun, 2022
Submission checks completed at journal
10 Jun, 2022
Unknown event
09 Jun, 2022
Editor assigned by journal
08 Jun, 2022
First submitted to journal
08 Jun, 2022

You are reading this latest preprint version

Hyperinflation and its Association with Successful Transition to Home Ventilator Devices in Infants with Chronic Respiratory Failure and Severe Bronchopulmonary Dysplasia

Status:

Journal Publication

Version 1

Abstract

Objective

Design/Methods:

Results

Conclusions

Figures

Introduction

Methods

Results

Discussion

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1