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.