当前位置: 首页 > 期刊 > 《美国医学杂志》 > 2005年第10期 > 正文
编号:11357387
Congenital chylothorax treated with octreotide
http://www.100md.com 《美国医学杂志》
     Department of Pediatrics, SSK Region Hospital and Medical Faculty of Gaziantep University, 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, born 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 μg/kg per hour and increased daily by 1 μg/kg per hour to 10 μg/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.

    Keywords: Congenital chylothorax; 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,[2],[3] congenital heart disease,[4] mediastinal malignancies,[5],[6] chromosomal abnormalities,[7] and H-type tracheoeophageal fistulas.[8]

    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, but surgical intervention, for example, pleuroperitoneal shunting,[9] pleurodesis,[6] or direct ligation of the thoracic duct[10] 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.[11]-[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 aiding resolution of traumatic chylothoraces in the adult and pediatric population. [13],[14],[15],[16],[17] Recently, it has been utilized in the treatment of congenital chylothorax successfully by Rasiah et al .[18] 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 delivery 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, cytomegalovirus, herpes simplex, human immunodeficiency virus) was not indicative of infection. The infant was lymphopenic (0.3 × 10 9/L) and neutropenic (0.8 × 10 9/L), the former persisting for 10 days.

    The infant was placed nil orally with nutrition administered intravenously. Chyle losses were replaced with 4.5% human albumin solution and fresh frozen plasma. The infant was extubated on day 6 into nasal Continuous (Constant) Positive Airway Pressure (CPAP). Fluid loss from 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 time were greater than 200 mL/day.

    Bilateral pleuroperitoneal shunts were considered but in order to avoid surgery, a decision to treat the infant with 10 days of an octreotide infusion was made. Octreotide was commenced on day 15, initially 0.5 μg/kg per hour and increased daily by 1 μg/kg per hour to 10 μg/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 prompt respiratory improvement 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 7th 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 enriched milk (Monogen) on day 7 of the octreotide treatment and weaned fully to normal cow's milk formula (S26, Wyeth) 2 weeks after commencing octreotide. The infant was mildly distended on the 3rd day of octreotide therapy but this subsided without alteration of treatment. She was normoglycemic during and after octreotide therapy. No other side-effects were noted and she remains well at 6 months of age.

    Discussion

    Congenital chylothorax is a rare condition,[19] it is the commonest cause of pleural effusion causing respiratory distress in the neonatal period.[20] Large lymphatic 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 prior to 35 weeks gestation, abnormal karyotype or additional congenital anomalies and hydrops fetalis are associated.[13],[21] The frequency of spontaneous resolution is unknown and some cases resolve with supportive management. Recalcitrant cases traditionally require surgical intervention (pleurodesis, pleural-peritoneal shunting),[21] which are also not entirely risk-free. Shunting failed in four of the five babies reviewed by Al-Tawil et al.[11] In a review of 15 patients treated with externalized pleuroperitoneal shunts, Wolff et al. found that shunt malfunction necessitating surgical intervention in six patients and two patients developed infections which required shunt removal.[12]

    Somatostatin is a polypeptide that is widely 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 treatment of acromegaly, intractable diarrhea in children, severe gastrointestinal (GI) bleeding in adults and children, GI fistulae, pancreatitis, metastatic carcinoid and vasoactive intestinal peptide secreting tumours. [22],[23],[24],[25] In newborn infants, octreotide has been used in the management of persistent hyperinsulinaemic states.[26]

    Somatostatin or its long acting analogue, octreotide, has been explored with increasing frequency in post-traumatic chylothoraces in the adult and pediatric population table1. [13],[14],[15],[16],[17],[18] The mechanism of action of somatostatin in chylothorax remains uncertain. Somatostatin causes mild vasoconstriction of splanchnic vessels and reduces gastric, pancreatic and intestinal secretions as well as intestinal absorption and hepatic venous flow, which collectively may act in concert to reduce chyle flow.[27] Canine studies have suggested that reduction of chylomicron synthesis and transport into the lymphatic duct occurs through perturbation in the splanchnic circulation,[28] hence resulting in somatostatin being equally beneficial in post-traumatic (with injured lymphatic tracts) as well as congenital (with normal lymphatic tracts). Somatostatin has been found to be relatively free of side-effects when used for chylothorax treatment in the pediatric population. Side-effects primarily relate to the suppressive actions on the gastrointestinal motility and secretions, with transient loose stools, nausea, flatulence, hypoglycaemia and liver dysfunction being the most commonly reported. Apart from a mildly distended abdomen, the patient did not have any side-effects from the octreotide infusion, however, caution is advised to patients prone to necrotizing enterocolitis because of the effects of somatostatin on splanchnic blood flow. It is also important to note that neither the dose nor form of somatostatin or octreotide is established for chylothorax treatment as shown in table1. We used octreotide because it is the most readily available preparation in Turkey. table1 shows that an improvement has been noted at 1-2 μg/kg per hour of infusion of octreotide but we commenced on a lower dose (0.5 μg/kg per hour) for safety reasons. A dose of 10 μg/kg per hour appears to be the threshold dose in which benefit is seen and doses above this do not seem to be helpful.

    Although we did not observe a candidly reciprocal dose for flow relationship between the octreotide infusion and chyle loss, this could have been due to various technical problems such as blocked chest drains or positioning of the infant. Nevertheless, the benefits appeared to persist even after cessation of the octreotide, as verified by ultrasonography. To the author's knowledge, there have been two reports of octreotide in the management of congenital chylothorax. It is of belief that this is the second reported case in which this treatment has been used successfully.

    Octreotide appears to have a good safety profile in newborn infants and remains a promising alternative to surgery for recalcitrant cases of chylothoraces. It could be considered for early treatment in infants who have a multitude of poor prognostic indicators (such as a hydropic premature infant with bilateral effusions) to ameliorate the clinical course. As case numbers are small, further multicenter studies are required to ascertain optimal dosing and preparation, for either somatostatin or octreotide in the treatment of congenital chylothoraces

    References

    1. Smeltzer DM, Stickler GB, Fleming RE. Primary lymphatic dysplasia in children: Chylothorax, chylous ascites, and generalised lymphatic dysplasia. Eur J Pediatr 1986; 45: 286-292.

    2. Levine C. Primary disorders of the lymphatic vessels-a unified concept. J Pediatr Surg 1989; 24 : 233-240.

    3. Hilliard RI, McKendry JB, Phillips MJ. Congenital abnormalities of the lymphatic system: a new clinical classification. Pediatr 1990; 86: 988-994.

    4. Adiotomre PN, Burns JE, McIntosh N. Hydrops foetalis and chylothorax associated with superior caval vein obstruction and resolution following balloon dilatation. Acta Pediatr 1994; 83: 983-985.

    5. Easa D, Balaraman V, Ash K, Thompson B, Boychuk R. Congenital Chylothorax and mediastinal neuroblastoma. Pediatric Surg 1991; 26: 96-98.

    6. Hesseling PB, Hoffman H. Chylothorax: a review of the literature and report of 3 cases. S Afr Med 1981; 60: 675-678.

    7. Ho NK, Leong NK, Lim SB. Chylothorax in Down's syndrome associated with hydrops fetalis. J Singapore Pediatr Soc 1989; 31: 90-92.

    8. Harvey JG, Houlsby W, Sherman K, Gough MH. Congenital Chylothorax: report of unique case associated with 'H-type tracheooesophageal fistula. Br J Surg 1979; 66: 485-487.

    9. Azizkhan RG, Canfield J, Alford BA, Rodgers BM. Pleuroperitoneal shunts in the management of neonatal chylothorax. J Pediatric Surg 1983; 18: 842-850.

    10. Anderson EA, Hertel J, Pedersen SA et al. Congenital chylothorax: Management by ligature of the thoracic duct. Scand J Thorac Cardiovasc Surg 1984; 18 : 193-194.

    11. Al-Tawil K, Ahmed G, Al-Hathal M, Al-Jarallah Y, Campbell N. Congenital chylothorax. Am J Perinatol 2000; 17 : 121-126.

    12. Wolff AB, Silen ML, Kokoska ER, Rodgers BM. Treatment of refractory chylothorax with externalised pleuroperitoneal shunts in children. Ann Thorac Surg 1999; 68: 1053-1057.

    13. Buettiker V, Hug MI, Burger R, Baenziger O. Somatostatin: A new therapeutic option for the treatment of chylothorax. Intens Care Med 2001; 27: 1083-1086.

    14. Rosti L, Bini RM, Chessa M, Butera G, Drago M, Carminati M. The effectiveness of octreotide in the treatment of postoperative chylothorax. Eur J Pediatr 2002; 161: 149-150.

    15. Cheung Y, Leung MP, Yip M. Octreotide for treatment of postoperative chylothorax. J Pediatr 2001; 139: 157-159.

    16. Pratap U, Slavik Z, Ofoe VD, Franklin R. Octreotide to treat postoperative chylothorax after cardiac operations in children. Ann Thorac Surg 2001; 72: 1740-1742.

    17. Lam JC, Aters S, Tobias JD. Initial experience with Octreotide in the pediatric population. Am J Ther 2001; 8: 409-415.

    18. Rasiah SV, Oei J, Lui K. Octreotide in the treatment of congenital chylothorax. J Pediatr Child Health 2004; 40: 585-588.

    19. Beghetti M, La Scala G, Belli D, Bugmann P, Kalangos A, Le Coultre C. Etiology and management of pediatric chylothorax. J Pediatrics 2000; 136: 653-658.

    20. Chernick V, Reed MH. Pneumothorax and chylothorax in the neonatal period. J Pediatrics 1970; 76: 624-632.

    21. Dubin PJ, King IN, Gallagher PG. Congenital Chylothorax. Curr Opin Pediatr 2000; 12: 505-509.

    22. Mulvihill S, Pappas TN, Passaro E Jr, Debas HT. The use of somatostatin and its analogs in the treatment of surgical disorders. Surgery 1986; 100: 467-475.

    23. Siafakas C, Fox VL, Nurko S. Use of octreotide for the treatment of severe gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr 1998; 26: 356-359.

    24. Tauber MT, Harris AG, Rochiccioli P. Clinical use of the long acting somatostatin analogue octreotide in pediatrics. Eur J Pediatr 1994; 153: 304-310.

    25. Lamberts SWJ, van der Lely AJ, de Herder WW, Hofland LJ. Drug therapy: Octreotide. N Engl J Med 1996; 334: 246-254.

    26. Glaser B, Hirsch HJ, Landau H. Persistent hyperinsulinemic hypoglycaemia of infancy: long-term octreotide treatment without pancreatectomy. J Pediatr 1993; 123: 644-650.

    27. Davis SN, Granner DK. Insulin, oral hypoglycaemic agents and the pharmacology of the endocrine pancreas. In AG Gilmand, JG Hardman, LE Limbird, PB Molionaff, RW Ruddon, eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 9th (edn). New York; Pergamon Press, 1996; 1512-1513.

    28. Nakabayashi H, Sagara H, Usukura N, Yoshimitsu K, Imamura T, Seta T, Yanase E, Kawato M, Hiraiwa Y, Sakato S, Takeda R. Effect of somatostatin on the flow rate and triglyceride levels of thoracic duct lymph in normal and vagotomised dogs. Diabetes 1981; 30 : 440-445.(Sahin Yasin, Aydin Derya)