Cl in ica l Br ief

Congenital Chylothorax Treated with Octreotide Yasin Sahin and Derya Aydin

Department of Pediatrics, SSK Region Hospital and Medical Faculty of Gaziantep Universitlj, Turkey

Abstract. Congenital chylothorax is the accumulation of lymphatic fluid within the pleural space. Cases unresponsive to conservative management usually require surgery. Octreotide has been used successfully to treat post-traumatic chylothoraces in the pediatric and adult population. Its exact mode of action is uncertain but it is believed to reduce lymphatic drainage by a direct action on splanchnic lymph flow. We report a case of congenital chylothorax where surgery was avoided with the compassionate trial of the somatostatin analogue, octreotide. A 33 week gestation female infant, 10om with the presence of large bilateral pleural effusion, was unresponsive to conservative management. Octreotide was commenced on day 15, with 10 days of an octreotide infusion, initially 0.5 pg/kg per hour and increased daily by 1 pg/kg per hour to 10 pg/kg per hour. Treatment was associated with prompt respiratory improvement prior to cessation of pleural drainage over the 10 day. She remains well at 6 months of age. Further studies are required to ascertain its true value in congenital chylothorax. [Indian J Pedlatr 2005; 72(10) : 885-888] E-maih pediatfistsahin@mynet.com

Key words : Congenital chy/othorax; Neonate; Octreotide

Chylothorax is the accumulation of chyle in the pleural space due to the disruption of the thoracic duct or its lymphatic tributary. Chylothoraces may be either acquired (usuaLly from trauma to the thoracic duct during surgery) or congenital, the latter of which is probably a result of in utero thoracic duct obstruction. 1

Congenital chylothoraces (CC) may be associated with abnormalities of the lymphatic system, for example, lymphangiomatosis and lymphangiectasia, z3 congenital heart disease, 4 mediastinal malign~ancies, s~ chromosomal abnormalities, 7 and H-type tracheoeophageal fistulas?

The optimal method of treatment remains controversial. Currently, conservative treatment includes the use of a low-fat high-protein diet, supplemented with medium chain triglycerides (MCT) or total parenteral nutrition (TPN) combined with pleural drainage. The frequency and timing of spontaneous resolution is variable, bu t surgical intervention, for example, pleuroperitoneal shunting,9 pleurodesis,6 or direct ligation of the thoracic duct 1~ has been attempted in older infants and adults if spontaneous resolution does not occur in about a month after onset of the chylothorax. Surgical interventions are not entirely risk free and not assuredly successful, and surgical intervention has failed in many cases, especially when associated with shunt malfunction or infection, n-12

Recent reports have suggested that somatostatin (or its longer acting synthetic analogue, octreotide), by value of its direct action on lymphatic flow, has been useful in

Correspondence and Reprint requests : Dr. Yasin Sahin, MD Giineykent Mah. 248 nolu Sok. Ugurevler B Blok Kat 3 Daire 10, 27060 Sahinbey, Gaziantep, Tiirkiye. Tel: 0342 338 17 31; GSM: 0532 60210 63. Fax: (0342) 338 8618.

aiding resolution of traumatic chylothoraces in the adult and pediatric population. 13-17 Recently, it has been utilized in the treatment of congenital chylothorax successfully by Rasiah et al. TM Herein, we report a case of congenital chylothorax in which resolution was aided with octreotide.

CASE REPORT

A 33 week gestation female infant, weighing 2350 g, was born by normal delivery to a 32-year-old multiparous (gravida 3, para 2) mother in the SSK Region Hospital of Gaziantep, Turkey. The pregnancy was uneventful apart from decreased fetal movements, 2 days prior to delivery. The infant was hydropic at del ivery and required ventilatory support immediately after birth. APGAR scores were 2 at 5 min and 4 at 10 min. Initial chest X-ray revealed the presence of large bilateral pleural effusion.

The infant was not dysmorphic. Bilateral intercostal drains were inserted and copious straw coloured fluid was drained (determined to be chyle from biochemical and cytological analysis: lactate dehydrogenase 85 U/L, total protein 15 g/L, cholesterol 0.7, triglyceride 0.3 (unfed), cytospin: neutrophils 3%, lymphocytes 95% and monocytes 2%). Combined chyle losses from both chest drains averaged 250 mL/day (100mL/kg per day) in the first week.

Chromosome analysis was normal. Echocardiogram revealed a patent ductus arteriosus that resolved with conservative management. There was no evidence of pericardial effusion. Inotropic support was required for the first 6 days of life. Abdominal and cranial ultrasound scans were normal. Viral serology (toxoplasma, rubella,

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Yasin Sahin and Derya Aydin

c y t o m e g a l o v i r u s , h e r p e s s implex , h u m a n immunodeficiency virus) was not indicative of infection. The in fan t w a s l y m p h o p e n i c (0.3 x 10 9 / L ) and neutropenic (0.8 x 10 9/L), the former persisting for 10 days.

The in fan t was p l aced nil o ra l ly wi th nu t r i t i on administered intravenously. Chyle losses were replaced wi th 4.5% h u m a n a lbumin solut ion and fresh frozen plasma. The infant was extubated on day 6 into nasal Continuous (Constant) Positive Airway Pressure (CPAP). Fluid loss f rom the right chest drain receded and that drain was removed on day 12, but left chest drain losses remained high, fluctuating between 50-125 mL most days. On day 14, there was a clinical and radiological evidence of reaccumulation of right pleural effusion, requiring re- ventilation on that day as well as subsequent reinsertion of the right chest drain. Chyle losses at that t ime were greater than 200 mL/day .

Bilateral pleuroperitoneal shunts were considered but in order to avoid surgery, a decision to treat the infant w i th 10 days of an oc t r eo t ide in fus ion was made . Octreotide was commenced on day 15, initially 0.5 lJg/kg per hour and increased daily by 1 t~g/kg per hour to 10 l~g/kg per hour. Nothwithstanding lack of drainage due to blocked tubes, chyle loss decreased over the 10 day period. Chest drains were removed 12 days later.

There was a p r o m p t resp i ra to ry i m p r o v e m e n t on commencement of octreotide. The infant was extubated 2 days after starting the therapy, and nasal CPAP was not needed. He was weaned to room air on the 7 th day of treatment but needed supplemental oxygen 2 days after cessation of the octerotide treatment for a further 4 days. The infant was commenced on medium chain triglyceride enr iched mi lk (Monogen) on day 7 of the octreot ide treatment and weaned fully to normal cow's milk formula ($26, Wyeth) 2 weeks after commencing octreotide. The infant was mildly distended on the 3 rd day of octreotide therapy but this subsided without alteration of treatment.

She was no rmog lycemic du r ing and after oct reot ide t he r apy . No o ther s ide-ef fec ts we re n o t e d and she remains well at 6 months of age.

DISCUSSION

Congeni ta l chylo thorax is a rare condit ion, TM it is the commonest cause of pleural effusion causing respiratory distress in the neonatal per iodY Large lymphat ic fluid losses result in hypoalbuminemia, electrolyte imbalance, clotting dysfunction and immune deficiencies. An overall mortality of congenital chylothorax up to 50% has been reported, with poor prognosis attached to cases where gestational age is less then 32 weeks at diagnosis, delivery pr ior to 35 weeks gestat ion, a b n o r m a l k a r y o t y p e or additional congenital anomalies and hydrops fetalis are associated. 13,21 The frequency of spontaneous resolution is u n k n o w n and some cases r e so lve w i th s u p p o r t i v e managemen t . Recalcitrant cases t radi t ional ly require surgical in tervent ion (pleurodesis, p leura l -per i toneal shunting), 21 which are also not entirely risk-free. Shunting failed in four of the five babies reviewed by A1-Tawil et

al. ~ In a review of 15 patients treated with externalized p leuroper i toneal shunts, Wolff et al. found that shunt malfunct ion necessi tat ing surgical in tervent ion in six pat ients and two patients deve loped infections which required shunt removaU 2

S o m a t o s t a t i n is a p o l y p e p t i d e tha t is w i d e l y distributed throughout the body with a mainly inhibitory effect on the gastrointestinal tract and endocrine systems. Somatostatin or its long acting analogue octreotide have been used in the t rea tment of acromegaly, intractable diarrhea in children, severe gastrointestinal (GI) bleeding in adults and children, GI fistulae, pancreatitis, metastatic carcinoid and vasoact ive intestinal pep t ide secreting tumours. 22-2s In newborn infants, octreotide has been used in the m a n a g e m e n t of pers i s ten t hype r in su l i naemic states. 26

TABLE 1. Studies Using Octreotide or Somatostatin as Treatment for Post-traumatic and Congenital Chylothorax

Author Treatment No. of Age of Method of Treatment Duration Failure Side effects patients patients (days)

Buettiker Somatostatin 4 Newborn- Infusion 3.5-101ag/kg 9-11 1 (Down Diarrhea 12 weeks per hour synd.) in 1 patient

resolved with decreasing rate

R o s t i Octreotide 6 Not 0.1-1~ag/kg per hour 10 Nil Nil mentioned

Cheung Octreotide 2 3 months 1040t~g/kg per day s/c 8 Nil Nil in three divided doses

Pratap Octreotide 4 2-4 years 1-4 pg/kg per hour 5 Nil Nil

Lam Octreotide 1 2 months 4.2 lag/kg per hour 7 Nil Nil

Rasiah Octreotide 1 Newborn 0.5 pg/kg per hour 10 Nil Nil

886 Indian Journal of Pediatrics, Volume 72--October, 2005

Congenital Chylothorax Treated with Octreotide

Somatostat in or its long acting analogue, octreotide, has been explored wi th increasing f requency in post- t r a u m a t i c c h y l o t h o r a c e s in the adu l t and p e d i a t r i c popu la t i on (Table 1). 13-1s The m e c h a n i s m of act ion of s o m a t o s t a t i n in c h y l o t h o r a x r e m a i n s unce r t a in . Somatostatin causes mild vasoconstriction of splanchnic vessels and reduces gastric, pancreat ic and intestinal secretions as well as intestinal absorpt ion and hepatic venous flow, which collectively m a y act in concert to reduce chyle flow. 27 Canine studies have suggested that reduction of chylomicron synthesis and transport into the l y m p h a t i c d u c t occurs t h r o u g h p e r t u r b a t i o n in the splanchnic circulation, ~ hence resulting in somatostatin being equally beneficial in post- traumatic (with injured lympha t i c tracts) as well as congeni ta l (with n o rma l lympha t i c tracts). Somatos ta t in has been found to be relatively free of side-effects when used for chylothorax t r e a t m e n t in the p e d i a t r i c p o p u l a t i o n . S ide-ef fec ts p r i m a r i l y r e l a t e to the s u p p r e s s i v e ac t ions on the gastrointestinal moti l i ty and secretions, with transient loose stools, nausea, flatulence, hypoglycaemia and liver dysfunction being the most commonly reported. Apar t f rom a mi ld ly dis tended abdomen, the pat ient did not h a v e a n y s ide-ef fec ts f r o m the oc t reo t ide infus ion , h o w e v e r , c au t i on is a d v i s e d to pa t i en t s p r o n e to n e c r o t i z i n g en te roco l i t i s b e c a u s e of the ef fec ts of s o m a t o s t a t i n on s p l a n c h n i c b l o o d f low. It is a lso i m p o r t a n t to no te tha t ne i ther the dose nor fo rm of somatostatin or octreofide is established for chylothorax treatment as shown in table 1. We used octreotide because it is the mos t readi ly available p repara t ion in Turkey. Table I shows that an improvement has been noted at 1- 2 p g / k g p e r h o u r of i n fus ion of oc t r eo t ide bu t we commenced on a lower dose (0.5 D g / k g per hour) for safety reasons. A dose of 10 lag/kg per hour appears to be the threshold dose in which benefi t is seen and doses above this do not seem to be helpful.

Al though we did not observe a candidly reciprocal dose for flow relationship between the octreotide infusion and chyle loss, this could h a v e been due to va r ious technical p r o b l e m s such as b l ocked chest d ra ins or pos i t i on ing of the infant . Never the less , the benef i t s appeared to persist even after cessation of the octreotide, as ve r i f i ed b y u l t r a s o n o g r a p h y . To the a u t h o r ' s knowledge, there have been two reports of octreotide in the management of congenital chylothorax. It is of belief tha t this is the s econd r e p o r t e d case in wh ich this treatment has been used successfully.

Octreotide appears to have a good safety profi le in newborn infants and remains a promising alternative to surgery for recalcitrant cases of chylothoraces. It could be cons idered for ear ly t r ea tment in infants who have a m u l t i t u d e of p o o r p r o g n o s t i c ind ica to r s (such as a hydropic p r ema tu re infant wi th bilateral effusions) to ameliorate the clinical course. As case numbers are small, fu r ther mul t i cen te r s tudies are required to ascer ta in optimal dosing and preparation, for either somatostatin or

octreotide in the treatment of congenital chylothoraces.

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