Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity, impacting 40% of infants born prior to 28 weeks. Multidisciplinary care models, such as the Newborn and Infant Chronic Lung Disease Program (NeoCLD Program) at Children’s Hospital of Philadelphia (CHOP), are integral in supporting infants with the most severe grade BPD. As the NeoCLD Program has grown, it is caring for an increasingly complex population with significant sequelae and evolving disease phenotypes. One particularly challenging complication that has emerged is BPD-associated acquired lymphatic dysfunction.
Here, we present a case of an infant referred to the NeoCLD Program and describe the multimodal management strategies used to optimize her care.
AB was born at 25 weeks’ gestation at an outside NICU. Because of her immaturity, she required invasive mechanical ventilation to support her delicate and underdeveloped lungs. Early in life, she developed pulmonary interstitial emphysema (PIE), requiring an extended course of high-frequency ventilation. After several weeks, she transitioned to a conventional ventilator; however, persistent hypoxia and hypercapnia required progressively higher ventilatory support, including PEEP levels in the teens. Her disease was refractory to several lung-targeted steroid courses, and evolving hyperinflation was noted on chest X-ray (CXR).
Over the first few months of life, there was increasing concern for preferential head and neck edema, which became especially evident by 42 weeks’ postmenstrual age (PMA). At that time, the care team at AB’s home hospital began discussing her case with Kathleen Gibbs, MD, Medical Director of the NeoCLD Program.
Workup at the outside hospital included a brain ultrasound (US) that was without evidence of intraventricular hemorrhage (IVH) or hydrocephalus, as well as a jugular US that demonstrated patent bilateral veins. Management included trials of lower ventilator pressures and diuretic therapy. Despite these efforts, the infant continued with progressive hypoxia and hyperinflation.
At 45 weeks PMA, AB’s medical needs exceeded the referring hospital’s scope, and she was transferred to CHOP for further management of grade 3 BPD and anasarca.
On admission to CHOP, the infant demonstrated frequent missed respiratory efforts on the ventilator which showed mechanics concerning for small airway obstruction. Imaging was concerning for global hyperinflation, and blood gas analysis revealed compensated hypercarbia. An echocardiogram obtained per CHOP pulmonary hypertension screening pathway was without evidence of pulmonary hypertension.
Inhaled medications were titrated to provide maximum bronchodilation, and a continuous diuretic infusion was initiated. Sedating medications were optimized, and the patient underwent a period of pharmacologic muscle relaxation to exclude patient-driven respiratory efforts as a contributing factor.
The Jill and Mark Fishman Center for Lymphatic Disorders was also consulted, and AB underwent dynamic contrast-enhanced MR lymphangiography (MRL). This imaging modality demonstrated an anatomically patent thoracic duct, but with functionally limited flow into the venous system which resulted in diffuse accumulation of lymphatic fluid in the skin — most notably in the head and neck — as well as additional dilated lymphatic channels.
Ventilator titration was performed during the study that allowed for identification of settings and pressures to optimize thoracic duct flow.
Over the course of several weeks, AB was stabilized on these new ventilator settings and stable diuresis was established. Low-fat feeds were introduced and tolerated well. Slow but consistent lung decompression was achieved, and the infant ultimately underwent tracheostomy placement.
AB continued to require highly specialized care and remained hospitalized for the first two years of her life. She was ultimately discharged home with her family after comprehensive tracheostomy and home ventilator teaching, with close outpatient follow-up.
Acquired lymphatic dysfunction represents a rare, but serious endophenotype of infants with severe BPD. The lymphatic system, which normally drains fluid and proteins via the thoracic duct, is disrupted by the elevated intrathoracic pressures associated with lung injury and invasive ventilatory support. As a result, lymphatic fluid has impaired drainage and often flows retrograde through channels that contribute to dermal, pleural and peritoneal backflow.
Clinical features include edema, often preferential to the head and neck, chylous effusions and ascites, as well as feeding intolerance that is a result of protein losing enteropathy (PLE).
Treatment options for these high-risk infants require extensive discussions between multiple subspecialties in order to establish an individualized care plan. Dynamic contrast-enhanced MR lymphangiography (MRL) enables identification of lymphatic perfusion abnormalities and can confirm the patency of the thoracic duct.
If there is loss of thoracic duct patency, for example due to thrombosis from an old central line, then surgical intervention is necessary to address the lymphatic dysfunction. In partnership with the Jill and Mark Fishman Center for Lymphatic Disorders, the NeoCLD Program has been utilizing a novel technique at the time of MRL that involves titration of ventilator settings to map out which settings optimize lymphatic flow. This gives the team a threshold of what settings and pressures begin to contribute to lymphatic dysfunction. In some cases during MRL, the lymphatic team may also identify additional beneficial interventions — for example, if large lymphatic channels in the head/neck are seen, a lymphatic procedure may optimize the safety and decrease the potential complications of future tracheostomy placement.
Partly limited by the recognition of BPD related lymphatic dysfunction as a diagnosis, we do not fully know it’s exact prevalence in the BPD population. However, it does seem to occur across a spectrum of severity. Adding to the management challenges, this disease process is highly unpredictable and, even with successful treatment strategies, these vulnerable patients will almost always require long-term specialized care.
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Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity, impacting 40% of infants born prior to 28 weeks. Multidisciplinary care models, such as the Newborn and Infant Chronic Lung Disease Program (NeoCLD Program) at Children’s Hospital of Philadelphia (CHOP), are integral in supporting infants with the most severe grade BPD. As the NeoCLD Program has grown, it is caring for an increasingly complex population with significant sequelae and evolving disease phenotypes. One particularly challenging complication that has emerged is BPD-associated acquired lymphatic dysfunction.
Here, we present a case of an infant referred to the NeoCLD Program and describe the multimodal management strategies used to optimize her care.
AB was born at 25 weeks’ gestation at an outside NICU. Because of her immaturity, she required invasive mechanical ventilation to support her delicate and underdeveloped lungs. Early in life, she developed pulmonary interstitial emphysema (PIE), requiring an extended course of high-frequency ventilation. After several weeks, she transitioned to a conventional ventilator; however, persistent hypoxia and hypercapnia required progressively higher ventilatory support, including PEEP levels in the teens. Her disease was refractory to several lung-targeted steroid courses, and evolving hyperinflation was noted on chest X-ray (CXR).
Over the first few months of life, there was increasing concern for preferential head and neck edema, which became especially evident by 42 weeks’ postmenstrual age (PMA). At that time, the care team at AB’s home hospital began discussing her case with Kathleen Gibbs, MD, Medical Director of the NeoCLD Program.
Workup at the outside hospital included a brain ultrasound (US) that was without evidence of intraventricular hemorrhage (IVH) or hydrocephalus, as well as a jugular US that demonstrated patent bilateral veins. Management included trials of lower ventilator pressures and diuretic therapy. Despite these efforts, the infant continued with progressive hypoxia and hyperinflation.
At 45 weeks PMA, AB’s medical needs exceeded the referring hospital’s scope, and she was transferred to CHOP for further management of grade 3 BPD and anasarca.
On admission to CHOP, the infant demonstrated frequent missed respiratory efforts on the ventilator which showed mechanics concerning for small airway obstruction. Imaging was concerning for global hyperinflation, and blood gas analysis revealed compensated hypercarbia. An echocardiogram obtained per CHOP pulmonary hypertension screening pathway was without evidence of pulmonary hypertension.
Inhaled medications were titrated to provide maximum bronchodilation, and a continuous diuretic infusion was initiated. Sedating medications were optimized, and the patient underwent a period of pharmacologic muscle relaxation to exclude patient-driven respiratory efforts as a contributing factor.
The Jill and Mark Fishman Center for Lymphatic Disorders was also consulted, and AB underwent dynamic contrast-enhanced MR lymphangiography (MRL). This imaging modality demonstrated an anatomically patent thoracic duct, but with functionally limited flow into the venous system which resulted in diffuse accumulation of lymphatic fluid in the skin — most notably in the head and neck — as well as additional dilated lymphatic channels.
Ventilator titration was performed during the study that allowed for identification of settings and pressures to optimize thoracic duct flow.
Over the course of several weeks, AB was stabilized on these new ventilator settings and stable diuresis was established. Low-fat feeds were introduced and tolerated well. Slow but consistent lung decompression was achieved, and the infant ultimately underwent tracheostomy placement.
AB continued to require highly specialized care and remained hospitalized for the first two years of her life. She was ultimately discharged home with her family after comprehensive tracheostomy and home ventilator teaching, with close outpatient follow-up.
Acquired lymphatic dysfunction represents a rare, but serious endophenotype of infants with severe BPD. The lymphatic system, which normally drains fluid and proteins via the thoracic duct, is disrupted by the elevated intrathoracic pressures associated with lung injury and invasive ventilatory support. As a result, lymphatic fluid has impaired drainage and often flows retrograde through channels that contribute to dermal, pleural and peritoneal backflow.
Clinical features include edema, often preferential to the head and neck, chylous effusions and ascites, as well as feeding intolerance that is a result of protein losing enteropathy (PLE).
Treatment options for these high-risk infants require extensive discussions between multiple subspecialties in order to establish an individualized care plan. Dynamic contrast-enhanced MR lymphangiography (MRL) enables identification of lymphatic perfusion abnormalities and can confirm the patency of the thoracic duct.
If there is loss of thoracic duct patency, for example due to thrombosis from an old central line, then surgical intervention is necessary to address the lymphatic dysfunction. In partnership with the Jill and Mark Fishman Center for Lymphatic Disorders, the NeoCLD Program has been utilizing a novel technique at the time of MRL that involves titration of ventilator settings to map out which settings optimize lymphatic flow. This gives the team a threshold of what settings and pressures begin to contribute to lymphatic dysfunction. In some cases during MRL, the lymphatic team may also identify additional beneficial interventions — for example, if large lymphatic channels in the head/neck are seen, a lymphatic procedure may optimize the safety and decrease the potential complications of future tracheostomy placement.
Partly limited by the recognition of BPD related lymphatic dysfunction as a diagnosis, we do not fully know it’s exact prevalence in the BPD population. However, it does seem to occur across a spectrum of severity. Adding to the management challenges, this disease process is highly unpredictable and, even with successful treatment strategies, these vulnerable patients will almost always require long-term specialized care.
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