Classifying multicenter approaches to invasive mechanical ventilation for infants with bronchopulmonary dysplasia using hierarchical clustering analysis.

INTRODUCTION: Evidence-based ventilation strategies for infants with severe bronchopulmonary dysplasia (BPD) remain unknown. Determining whether contemporary ventilation approaches cluster as specific BPD strategies may better characterize care and enhance the design of clinical trials. The objective of this study was to test the hypothesis that unsupervised, multifactorial clustering analysis of point prevalence ventilator setting data would classify a discrete number of physiology-based approaches to mechanical ventilation in a multicenter cohort of infants with severe BPD. METHODS: We performed a secondary analysis of a multicenter point prevalence study of infants with severe BPD treated with invasive mechanical ventilation. We clustered the cohort by mean airway pressure (MAP), positive end expiratory pressure (PEEP), set respiratory rate, and inspiratory time (Ti) using Ward's hierarchical clustering analysis (HCA). RESULTS: Seventy-eight patients with severe BPD were included from 14 centers. HCA classified three discrete clusters as determined by an agglomerative coefficient of 0.97. Cluster stability was relatively strong as determined by Jaccard coefficient means of 0.79, 0.85, and 0.77 for clusters 1, 2, and 3, respectively. The median PEEP, MAP, rate, Ti, and PIP differed significantly between clusters for each comparison by Kruskall-Wallis testing (p < 0.0001). CONCLUSIONS: In this study, unsupervised clustering analysis of ventilator setting data identified three discrete approaches to mechanical ventilation in a multicenter cohort of infants with severe BPD. Prospective trials are needed to determine whether these approaches to mechanical ventilation are associated with specific severe BPD clinical phenotypes and differentially modify respiratory outcomes.

Transition from intensive care unit to a portable ventilator in children with severe bronchopulmonary dysplasia.

As the population of ventilator-dependent children (VDC) with tracheostomies due to underlying severe bronchopulmonary dysplasia grows, there is an increasing need to shift the care of these children from hospital to home. Transitioning the ventilator-dependent child from the hospital to home is a complex process that requires coordination between the medical team and the family. One crucial step in the process is transitioning from an Intensive care unit (ICU) ventilator to a portable home ventilator (PHV). The Clinical team needs to understand the nuances in transitioning to PHV, including assessing readiness to transition and choosing the optimum settings on an available home ventilator. In recent years, various ventilator modes have been available in PHV that can help achieve synchronous breathing to allow for adequate gas exchange for the infant. This review details some approaches to asses readiness to transition and the process of Transition along with commonly used modes of support available in PHV, as well as the primary and secondary settings in which we should be mindful in supporting a child with chronic respiratory failure in the home setting.

Ventilatory Strategies in Infants with Established Severe Bronchopulmonary Dysplasia: A Multicenter Point Prevalence Study.

We performed a point prevalence study on infants with severe bronchopulmonary dysplasia (BPD), collecting data on type and settings of ventilatory support; 187 infants, 51% of whom were on invasive positive-pressure ventilation (IPPV), from 15 centers were included. We found a significant center-specific variation in ventilator modes.

Proportional assist and neurally adjusted ventilation: Clinical knowledge and future trials in newborn infants.

Different types of patient triggered ventilator modes have become the mainstay of ventilation in term and preterm newborn infants. Maintaining spontaneous breathing has allowed for earlier weaning and the additive effects of respiratory efforts combined with pre-set mechanical inflations have reduced mean airway pressures, both of which are important components in trying to avoid lung injury and promote normal lung development. New sophisticated modes of assisted ventilation have been developed during the last decades where the control of ventilator support is turned over to the patient. The ventilator detects the respiratory effort and adjusts ventilatory assistance proportionally to each phase of the respiratory cycle, thus enabling the patient to have full control of the start, the duration and the amount of ventilatory assistance. In this paper we will review the literature on the ventilatory modes of proportional assist ventilation and neurally adjusted ventilatory assistance, examine the different ways the signals are analyzed, propose future studies, and suggest ways to apply these modes in the clinical environment.

Severe bronchopulmonary dysplasia: outcomes before and after the implementation of an inpatient multidisciplinary team.

OBJECTIVE: Severe bronchopulmonary dysplasia (sBPD) can lead to long term morbidity. We created a sBPD multidisciplinary team in 2011 to optimize care and improve outcomes. STUDY DESIGN: Retrospective chart review of three groups between 2008 and 2016: patients with sBPD born before 2011, patients with sBPD born after 2011, and patients with moderate BPD born after 2011. RESULTS: Infants with sBPD after 2011 had a shorter NICU length of stay compared with children born before 2011 (mean 140 days vs 170 days p < 0.007), weighed more at discharge (z-score -0.8 vs -1.35 p = 0.01), had less failure to thrive post discharge (32% vs 51% p = 0.05) and had more well visits in the first six months of life (mean 6.7 vs 5.3 p = 0.04). No difference was observed in the rate of readmissions in the first two years of life. CONCLUSION: Our multidisciplinary team has improved the inpatient management of patients with sBPD.

Multicenter Experience with Neurally Adjusted Ventilatory Assist in Infants with Severe Bronchopulmonary Dysplasia.

OBJECTIVE: The aim of this study is to determine patterns of neurally adjusted ventilatory assist (NAVA) use in ventilator-dependent preterm infants with evolving or established severe bronchopulmonary dysplasia (sBPD) among centers of the BPD Collaborative, including indications for its initiation, discontinuation, and outcomes. STUDY DESIGN: Retrospective review of infants with developing or established sBPD who were placed on NAVA after ≥4 weeks of mechanical ventilation and were ≥ 30 weeks of postmenstrual age (PMA). RESULTS: Among the 13 sites of the BPD collaborative, only four centers (31%) used NAVA in the management of infants with evolving or established BPD. A total of 112 patients met inclusion criteria from these four centers. PMA, weight at the start of NAVA and median number of days on NAVA, were different among the four centers. The impact of NAVA therapy was assessed as being successful in 67% of infants, as defined by the ability to achieve respiratory stability at a lower level of ventilator support, including extubation to noninvasive positive pressure ventilation or support with a home ventilator. In total 87% (range: 78-100%) of patients survived until discharge. CONCLUSION: We conclude that NAVA can be used safely and effectively in selective infants with sBPD. Indications and current strategies for the application of NAVA in infants with evolving or established BPD, however, are highly variable between centers. Although this pilot study suggests that NAVA may be successfully used for the management of infants with BPD, sufficient experience and well-designed clinical studies are needed to establish standards of care for defining the role of NAVA in the care of infants with sBPD.

The BIT:S (Bronchopulmonary Dysplasia Interdisciplinary Team: Severe) Initiative at Women and Infants Hospital of Rhode Island.

Bronchopulmonary dysplasia (BPD) is a major cause of morbidity and mortality in surviving extremely preterm infants, with long-term morbidity disproportionately affecting children with severe BPD (sBPD). Infants with sBPD experience multiple organ system dysfunction. To best treat these complicated patients, we created a multidisciplinary team in 2011 consisting of multiple pediatric subspecialists with a specific interest in sBPD. In the past six years, 150 patients have been referred to our multidisciplinary team, with 131 of the 150 patients discharged home, 65% on home oxygen. Twelve were transferred to the Pediatric Intensive Care Unit (PICU), 3 to a level 2 nursery and 4 died. The multidisciplinary BPD team has standardized the care of children with sBPD and complex medical problems and improved outpatient referral to subspecialists.

Systemic interleukin-6 responses following administration of adenovirus gene transfer vectors to humans by different routes.

Administration of adenovirus (Ad) vectors to animals induces innate immune responses, typified by elevated interleukin-6 (IL-6). To assess innate responses to Ad vectors in humans, we evaluated serum IL-6 following administration of E1(-) E3(-) Ad vectors to different human hosts and the relationship among peak IL-6 and peak anti-Ad neutralizing antibodies. We administered: 1) Ad(GV)CFTR.10, a vector carrying the normal human CFTR cDNA (3 x 10(7) to 2 x 10(10) particle units (pu)) to airways of individuals with cystic fibrosis (CF); 2) Ad(GV)VEGF121.10, a vector carrying the normal human vascular endothelial growth factor (VEGF)121 cDNA, to the myocardium (4 x 10(8) to 4 x 10(10) pu) of individuals with coronary artery disease (CAD) and to lower extremity muscles (4 x 10(8) to 4 x 10(9.5) pu) of individuals with peripheral vascular disease (PVD); and 3) Ad(GV)CD.10, a vector carrying the Escherichia coli cytosine deaminase gene to skin (7 x 10(7) to 7 x 10(9) pu) and airways (7 x 10(8) to 7 x 10(10) pu) of normal individuals and to liver metastasis (4 x 10(8) to 4 x 10(9) pu) of individuals with colon carcinoma. IL-6 increased mildly (up to 220 pg/ml) following vector administration to skin and lung airways of normal individuals and of individuals with CF, and to muscle and liver metastasis of individuals with PVD and colon cancer, respectively. IL-6 responses were higher (up to 1100 pg/ml) following myocardial administration. Control individuals who had chest surgery and bronchoscopy, but no vector administration, had comparable IL-6 increases. Thus, both administration of Ad vectors of humans up to 10(10) pu and the procedures used to administer the vectors elicit systemic IL-6 responses. There was no correlation among peak IL-6 and peak anti-Ad antibodies. These observations indicate that the innate host responses following administration of Ad vectors to humans may result from the procedures used to administer the vector, and from the vector per se.