Successful treatment of congenital chylothorax with skimmed milk and long course octreotide

Abstract

Congenital chylothorax (CC) is a rare entity in neonatal period requiring multimodal management strategies. Despite optimum treatment, some cases remain refractory posing significant challenge to the treating physician. We here describe a 33-week preterm neonate presenting with refractory congenital chylothorax who needed treatment with combination of skimmed milk, high dose and prolonged duration octreotide for resolution. This case highlighted that octreotide has a good safety profile in newborn infants with congenital chylothorax and locally available skimmed milk fortified with medium chain triglyceride (MCT) oil is a cheap and safe alternative.

Background

Reported incidence of congenital chylothorax (CC) is 1 per 10 000–15 000 live births.¹ The presentation varies from hydrops in the antenatal period to severe respiratory failure in the neonatal period. Postnatal treatment is often multimodal and complex, and includes a varied combination of thoracocentesis, total parenteral nutrition (TPN), restriction of long-chain fatty acids and feeding with medium chain triglyceride (MCT)-based formula. Short course injection octreotide is reserved for those cases who do not respond to first-line therapy. We hereby describe a case which required octreotide therapy for 6 weeks along with skimmed milk fortified with MCT oil.

Case presentation

Index case was born at 33⁺⁶ week gestation with antenatal diagnosis of non-immune hydrops. Antenatal investigations were normal (box 1). The neonate required extensive resuscitation and thoracentesis in the delivery room. Early rescue surfactant was given at 1 hour of life followed by ongoing mechanical ventilation for 15 days (initial 3 days high-frequency ventilation) and inotropic support for 72 hours. During hospital stay, she had recurrent pleural fluid collections requiring multiple aspirations. Initial two pleural taps done in first 72 hours revealed straw colour fluid with cell count and biochemical analysis suggestive of transudate (table 1). However, these were done prior to initiation of oral feeds. Postnatal extensive aetiological workup turned normal. Repeat pleural fluid analysis done on days 6 and 13 while the baby was on predominant oral feeds suggested gross appearance like chyle along with confirmatory biochemical parameters (table 1). Postnatal confirmation of CC requires presence of >1000 cells⁄µL with at least 80% lymphocytes and >110 mg⁄dL of triglycerides in pleural fluid.²

Box 1. Investigations for aetiology of non-immune hydrops.

Antenatal investigations

Level II ultrasound: normal

Fetal echocardiodiography: normal

Metabolic workup for Gaucher disease, Niemann Pick A&B disease, nucopolysaccharidosis VII: normal

Postnatal investigations

G6PD: normal

Baby blood group: O+ve

Direct Coomb’s test: negative

Peripheral smear: no evidence of haemolysis

Parvovirus DNA PCR: negative

Venereal Disease Research Laboratory test (VDRL): negative

Toxoplasmosis, rubella cytomegalovirus, herpes simplex, and HIV (TORCH) profile: negative

Echocardiography: normal structure and function

Thyroid function test: normal

Lipid profile: normal values: low-density lipoprotein (LDL) 95 mg/dL, high-density lipoprotein (HDL) 28 mg/dL, triglyceride 52 mg/dL, LDL/HDL ratio: 3.25, very low density lipoprotein 9 mg/dL(normal range 10–30) and total cholesterol 128 mg/dL

Hb electrophoresis: HbA2 10%, Hb F 90%

Blood culture: sterile

Ultrasound abdomen: mild ascites

Urine for protein: negative

Fundus: no cherry red spots

Contrast-enhanced chest tomography: no evidence of congenital lung malformation

Renal function test (RFT): normal

Table 1.

Pleural fluid characteristics

Day of life	Protein (g/dL)	Sugar (mg/dL)	Cells	Culture	Pleural TG (mg/dL)	Cholesterol (mg/dL)
1	2.5	76	75 (P75, L25)	Sterile	–	128
6	0.5	86	900 (P10, L90)	Sterile	784	–
13	2	103	2800 (P20, L80)	Sterile	–	–
15	2.4	87	80 (L100)	Sterile	–	–

Treatment

The neonate was kept nil per oral (NPO). TPN was initiated. Intermittent albumin transfusions were ensured to overcome protein loss due to multiple pleural taps. Gradually simyl-MCT-based formula was introduced as it is hypothesised that medium-chain triglycerides are directly absorbed in to the portal system, bypassing the intestinal lymph system, thus reducing chyle production. However, on day 13 of life, she had worsening respiratory distress requiring repeat pleural tap. Thus, in view of repeated recollection of chylous fluid despite providing MCT-based formula, possibility of refractory chylothorax was kept. So intravenous octreotide infusion was started (day 15), initially at a low dose (1 μg/kg/hour; continuous infusion) for initial 3 days and later changed to intermittent subcutaneous doses @ 10 μg/kg/day (in three divided doses). She responded to medication initially and chylothorax resolved. However, there was reaccumulation of chyle after 6 days mandating reinitiation and hike in octreotide (subcutaneous) dose up to 30 μg/kg/day. Simultaneously simyl-MCT-based feed was continued. The response to the above combination therapy was however suboptimal. The possible explanation for suboptimal response to the above combination therapy seems the non-availability of a standardised simyl-MCT-based formula available in our country (100 mL of constituted formula provides around 0.26 g of MCT); hence the same was discontinued. Instead, locally available low-fat skimmed milk (with standard fat content of 0.1 g/100 mL) fortified with MCT oil (9 kcal/g) was introduced gradually and thereafter hiked. This time clinical response was evident and respiratory support could be gradually weaned off. She was finally discharged at postnatal age of 50 days on octreotide (subcutaneous) and locally available skimmed milk. She received octreotide injection for 6 weeks (4 weeks in hospital and 2 weeks at home). Serial liver function tests (LFT) and RFT were normal.

Outcome and follow-up

During follow-up, there was no reaccumulation of pleural effusion with normal weight gain and development. After 6 months, normal complimentary feeding was introduced which she tolerated well.

Discussion

CC is defined as accumulation of lymphatic fluid or chyle in the pleural space. Of the available approaches in management (which includes a combination of interventions like restriction or temporary cessation of enteral feedings, use of pleural drain, TPN and octreotide), no modality is superior.³ Octreotide seems the most widely used therapy for CC. It is believed to decrease splanchnic blood flow in thoracic duct as well as decrease triglyceride content of chyle by various mechanism.^3–5 However, there is no consensus on the optimal dose and duration of therapy. A Cochrane meta-analysis (2010) of 19 isolated cases of CC suggests a broad dose range of 20–70 μg/kg/day through subcutaneous route and 0.3–10 μg/kg/hour in intravenous route.⁶ Another recent systematic review in 2018 by Bellini et al also revealed similar variation of dose and duration.⁵ The longest reported duration of octreotide by subcutaneous route has been reported as 20 days.⁷ Our index case received subcutaneous octreotide for 6 weeks, which is the longest reported duration. In this unique case, we used a longer duration and a higher dose of subcutaneous octreotide compared with previously reported cases. Although adverse effects like constipation or diarrhoea, hyperglycaemia and hypoglycaemia have been reported,^{8 9} the same were not seen in our index case.

Aetiological workup of CC needs to be individualised as per clinical presentation. In our index case, pleural tap was performed at birth. It was transudate initially, while subsequent taps after initiation of oral feeds confirmed true chylous nature of fluid. Although lymphangiography or lymphoscintigraphy for localisation of aberrant lymphatics was warranted, these studies could not be performed in our index case due to feasibility issues in small neonate.

On resolution of the effusion, enteral feeds need to be started using low-fat or fat-free milk formulas which are costly, not freely available and non-standardised in resource-poor countries. Human milk has long-chain triglycerides, hence is not recommended. Skimmed milk preparation with coconut oil (rich in medium-chain triglyceride) could be a cheap and effective alternative in CC where other feeding options have failed or standardised commercial formulas are not accessible. The index case highlighted that higher dose and longer course subcutaneous octreotide can be safely used in cases of refractory CC. Nevertheless, occasional spontaneous resolution of CC in postnatal period without any therapy is a known fact which cannot be fully ignored in our case.

In summary, octreotide seems to have a good safety profile in newborn infants and remains a promising alternative to surgery for cases of CC. Locally available skimmed milk fortified with MCT oil is a safe and cheap alternative when the usual therapy fails.

Learning points.

• Congenital chylothorax management is often challenging for physicians.

• Long-course octreotide should be reserved for refractory cases.

• Locally available skimmed milk fortified with MCT oil can act as a safe alternative to surgery in difficult to treat cases.