INTRODUCTION
Chylothorax is the accumulation of chyle or lymphatic fluid in the pleural space. While rare in children, chylothorax is a significant cause of respiratory morbidity and can lead to depletion of fluids, proteins, immunoglobulins, and lymphocytes, eventually leading to malnutrition and immunodeficiency.1,2 There are five main etiologies: congenital, traumatic, high central venous pressure, malignancies, and miscellaneous (which includes infections).1,3,4 Patients with chylothorax often present with respiratory symptoms including dyspnea, cough, and non-pleuritic chest pain. In traumatic causes of chylothorax, patients can have cardiorespiratory symptoms due to rapid chyle accumulation in the pleural cavity. However, in nontraumatic causes the symptoms have a slower onset and progression.5
Typically, treatment of large pleural or lymphatic effusions involves a chest tube with quantification guiding management. Many hospitals use drainage output as a guide to quantify clinical improvement or failure (<10 mL/kg per day of pleural drainage is considered improvement; >10 mL/kg per day of pleural drainage is considered failure after four weeks of nonsurgical management).3,6
Management for chylous effusion further includes dietary modifications to limit chyle-forming elements in the diet. Dietary management requires a fat-free diet with medium-chain triglycerides, available as enteral formulas or total enteric rest requiring total parenteral nutrition, which is a more aggressive option.1 Use of conservative enteral or complete parenteral nutrition for one to three weeks resulted in resolution of the chylothorax in 80% of the patients if the effusion was not secondary to lymphatic anomalies6. However, if the effusion is due to a “mal”-formation in the lymphatic vasculature, placing the patient “nothing per oral” (NPO) is not sufficient as the effusion will persist but will not be chylous anymore. In these cases, while diet is useful in treatment, patients rarely have chylothorax resolution with diet alone.
Traditionally, octreotide has been the first-line pharmacologic treatment. In Shah and Sinn’s study, five of six patients with congenital chylothorax had resolution of effusion with octreotide with a median treatment of 20 days.7 In a systemic literature review of 35 children with chylothorax who were given octreotide, Roehr et. al found most studies reported a significant decrease in drainage within five to six days.8 While there are studies noting its efficacy, larger studies have found equivocal results. In a 2017 study of 178 neonates with chylothorax, Church, et. al found the addition of octreotide to dietary management of chylothorax revealed no significant differences in any outcome including success.9 Stated otherwise, octreotide added no measurable benefit over dietary management. Likewise, a 2010 Cochrane review of twenty case reports (no randomized controls identified) noted resolution of chylothorax in 14 of 20 neonates with treatment with octreotide; however, the researchers found no drastically beneficial effect.10
New alternatives such as sirolimus are now increasingly being utilized. Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor derived from Streptomyces hygroscopicus . Because of the role of mTOR in cell proliferation and angiogenesis, an overactive mTOR pathway due to activating mutations of its components has been implicated in diabetes, cancer, neurological diseases, genetic disorders, vascular anomalies and lymphatic anomalies.11 Sirolimus is considered a strong agent against lymphatic anomalies given its part in cell growth regulation and in the vascular endothelial growth factor (VEGF) pathway.1 Sirolimus has been shown to significantly reduce lesion size in tuberous sclerosis and lymphangioleiomyomatosis, which both involve mutations upstream from mTOR.12
A recent systematic review of sirolimus as a treatment for lymphatic malformations found that treatment with sirolimus led to a partial remission of disease in 60 of 71 patients studied (three patients had progressive disease and eight patient outcomes were not reported).11 While sirolimus is currently being used in treatment of chylothorax, its use and efficacy need continued studying to create better treatment guidelines.