DISCUSSION
Our study focuses on lymphatic effusions caused by complicated lymphatic
anomalies (CLAs) which included, in our series, generalized lymphatic
anomaly (GLA) and central conducting lymphatic anomaly (CCLA). The
average duration of sirolimus treatment needed for chest tube removal
was 16 days in our patient cohort. This is shorter than what has been
reported in previous studies with other interventions.
Use of conservative enteral or complete parenteral feeding for one to
three weeks may result in resolution of the chylothorax when the
effusion is not due to a lymphatic anomaly6. However,
in patients with significant chylothorax and associated respiratory
compromise (such as the patients described in our study) especially if
the patient is too clinically unstable to completely image the lymphatic
vasculature, conservative treatment alone is not adequate. Additionally,
chylous effusions can lead to malnutrition and immunodeficiency due to
loss of proteins and immunoglobulins in the chylous fluid. Given the
associated complications, it is imperative to reduce the amount of
pleural effusion promptly to alleviate the resulting respiratory
compromise.
Octreotide has been the traditional pharmacologic treatment for
chylothorax. A 2010 Cochrane Review and a 2017 study by Church et al.
both found no significant benefit of the addition of octreotide to
treatment regimens.9,10 Although, it is important to
note smaller studies illustrate its efficacy.7,8 In
our study, there were two patients (28.6%) who failed octreotide
treatment prior to sirolimus initiation. The other five patients were
started on sirolimus from the beginning due to confirmed or presumed
lymphatic etiology.
This study validates previous studies which showed sirolimus led to
partial remission of lymphatic disease.11,13 A phase
II clinical trial titled Safety and Efficacy Study of Sirolimus in
Complicated Vascular Anomalies (n=61 patients) with 57 evaluable cases
showed that 47 patients had a partial response, 3 developed stable
disease and 7 - progressive disease. Only two patients required
sirolimus discontinuation due to persistent adverse
effects.13 There are several case reports noting the
reduction of lymphatic effusions post sirolimus treatment with an
average time of 25 days to chylothorax
resolution.14-19 Based on our limited study
population, response to sirolimus appears to be faster than previously
reported.
Since this is a single center study, it is limited by a small size.
While twenty patients were originally considered within the study
criteria, inadequate chest tube drainage data and death prior to chest
tube removal narrowed the study population to seven. All seven were
critically-ill infants with a multitude of comorbidities. The clinical
course for all these patients varied widely due to their disparities in
age, and comorbidities. The incongruency in patients limits the
extendibility of the research. Additionally, the study was limited by
the variable data points of both sirolimus level and chest tube output.
Future studies could be improved by measuring sirolimus at regular
intervals post-initiation. Though efforts were made to quickly find
appropriate dosing of sirolimus, the patients studied were at times
subtherapeutic or supratherapeutic (which corresponded with changes in
chest tube output). Tighter control of sirolimus levels would aid in
finding the appropriate therapeutic range of sirolimus. To better
control the confounding factors of the study, exclusion factors could be
added to exclude patients with previous medical interventions (such as
octreotide).
In conclusion, our study shows that with close monitoring, sirolimus is
a safe and effective therapy for pediatric chylous effusions even in
critically ill infants. Due to the rare incidence of the condition, our
conclusion is based on a small case series. Larger multi-institutional
studies will be needed to further support and confirm these findings.