Case Study: The Fluid Filled Lung Oxygenation Assistance Trial

An ex 24-week infant was delivered at a community hospital with a birth weight of 490 grams. Pregnancy was a result of in vitro fertilization and complicated by preeclampsia. Mother received betamethasone prior to delivery, which was done via c-section secondary to preeclampsia. The infant was intubated at delivery and received surfactant.

Outside hospital course was notable for a patent ductus arteriosus ligation at 3 weeks of age, medical necrotizing enterocolitis, and concern for worsening retinopathy of prematurity (ROP). Respiratory course was also significant for 2 courses of dexamethasone DART (Dexamethasone: A Randomized Trial) protocol, however, the infant remained intubated for the majority of his outside hospital course. He was extubated for only a few days prior to transport, but reintubated for worsening hypoxia and hypercapnia. The infant was transferred to Children’s Hospital of Philadelphia (CHOP) for further evaluation and management of his ROP.

At the time of transfer the infant was 32 weeks corrected gestational age (CGA) and 910 grams. He was on conventional ventilation with a guaranteed tidal volume of 5 ml/kg, positive end-expiratory pressure (PEEP) of 7, rate of 45, and an oxygen requirement around 35%. His respiratory medications included furosemide and caffeine. Infant was given Avastin® injections for his ROP, with improvement. However, over several weeks it became evident that his lung disease was not trivial and was progressing.

A second trial of extubation was attempted around 2 months of age, but the infant failed within 24 hours due to significant work of breathing. A CT-angiogram at 4 months of age showed lung parenchymal disease consistent with chronic lung disease (CLD) of prematurity without evidence of pulmonary hypertension. A bronchoscopy around the same time was concerning for airway malacia. The infant was also treated for pseudomonas tracheitis at 3 months and 6 months of age.

Given the severity of his lung disease and perceived needs of prolonged mechanical ventilation, at 6 months of age (around 50 weeks CGA) the parents were approached about tracheostomy placement. The parents elected to participate in the Fluid Filled Lung Oxygenation Assistance Trial (FFLOAT) first and then would consider tracheostomy.

About the trial

At its current state, the FFLOAT trial is designed to assess the safety of an innovative partial liquid ventilation with perfluorooctyl bromide (PFOB) therapy in infants with severe CLD. In Part 1 of this study, infants are randomized (3:1) to either PFOB or a control (routine care) group for 5 days.

This study has been carefully reviewed by the Food and Drug Administration (FDA) and granted Investigational New Drug (IND) status for the study of liquid ventilation in neonates to William Fox, MD, Medical Director of CHOP’s Infant Breathing Disorder Center, and part of CHOP's Newborn and Infant Chronic Lung Disease Program team. This study is the result of a 25-year effort by Dr. Fox to bring back liquid ventilation to infants.

This infant was randomized to the PFOB group and received a total of 10 ml/kg of PFOB. Over the course of several weeks, the infant’s oxygen requirements decreased and he was able to wean on conventional ventilator settings. Following a fourth course of DART—approximately 3 weeks after the completion of the FFLOAT trial—the infant was extubated.

At the time of this report, he is slowly weaning on noninvasive respiratory support with only a minimal (~ 22%) oxygen requirement. Although he has been managed on post-pyloric feeds to minimize aspiration risk and further lung damage, reflux remains an issue for the infant. He underwent G-tube placement with Nissen fundoplication about 2 weeks ago and was extubated postoperatively without difficulty.

Summary

This case highlights the importance of research and the continued need for investigation into viable and innovative treatment options for this complex and severe disease. Our CLD patients are some of the most ill and vulnerable patients, and at present we have few treatments that can alter the long-term course of this complicated illness.

The focus of our research is not only to promote long-term survival of these infants, but to decrease disability and minimize morbidities. We continue to promote research in our multidisciplinary Newborn and Infant CLD Program in an effort to enhance the treatment of infants’ disease while focusing on enriching their lives as a whole.