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.