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Use of an Alpha-1 Adrenoreceptor Agonist in the Management of Recurrent Refractory Idiopathic Chylothorax

2018; Elsevier BV; Volume: 154; Issue: 1 Linguagem: Inglês

10.1016/j.chest.2018.02.005

1931-3543

Parthipan Sivakumar, Liju Ahmed,

Myasthenia Gravis and Thymoma

A 70-year-old woman presents with recurrent idiopathic chylothorax refractory to both medical and surgical treatment. To our knowledge, this is the first reported case where midodrine, an alpha-1 receptor agonist, was used as an adjunctive therapy for idiopathic chylothorax resulting in both a radiographic and clinical response. A 70-year-old woman presents with recurrent idiopathic chylothorax refractory to both medical and surgical treatment. To our knowledge, this is the first reported case where midodrine, an alpha-1 receptor agonist, was used as an adjunctive therapy for idiopathic chylothorax resulting in both a radiographic and clinical response. A 70-year-old woman presented to the hospital with worsening fatigue and breathlessness. She had a medical history of breast cancer treated with surgery and chemotherapy 17 years prior to her presentation. Her chest radiograph demonstrated a right pleural effusion (Fig 1A), and she underwent an ultrasound-guided thoracocentesis yielding milky white fluid with a triglyceride level of 20.29 mmol/L, consistent with a chylothorax. However, CT scan failed to identify a cause, with no evidence of breast cancer recurrence. During a protracted 7-month admission, she underwent multiple interventions. This included total parenteral nutrition, octreotide, multiple ascitic drains for chyloperitoneum, and failed attempts at local anaesthetic thoracoscopic talc pleurodesis on both sides. Pleural biopsies were benign, and three attempts at CT lymphangiography failed to identify a source for the leak. She therefore underwent thoracic duct ligation and at surgery the cisterna chyli was seen to herniate through the diaphragm (Fig 2). Despite ligation, she required a further laparoscopic resection of the paraaortic and coeliac truck lymphatics to stop the leak and she was discharged home. (Fig 1B).Figure 2Views at thoracoscopic surgery—the cisterna chyli herniating through the diaphragm.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Eight months later, her breathlessness returned. Chest radiograph confirmed a new left-sided pleural effusion with increase in size of the right-sided collection (Fig 3A). Pleural aspiration of the left side confirmed a chylous effusion. There was no evidence of ascites on this occasion. Repeat CT imaging again failed to demonstrate a cause and confirmed that her breast cancer remained in remission. She was admitted to hospital for left-sided thoracoscopy and iodine pleurodesis. This was unsuccessful with an average output of > 300 mL/d from her left-sided chest drain. Talc slurry pleurodesis via the existing drain was attempted 48 h later; however, the drain output did not decrease. Octreotide was not used because of the lack of response during her previous admission. Based on a case report of treatment success with the alpha-1 agonist, midodrine, in postoperative thoracic duct injury,1Liou D.Z. Warren H. Maher D.P. et al.Midodrine: a novel therapeutic for refractory chylothorax.Chest. 2013; 144: 1055-1057Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar oral midodrine was commenced, uptitrating the dose to a maximum of 10 mg four times daily. After 48 h of therapy, the drain output reduced to 150 mL/d, the drain was removed, and she was discharged with close outpatient follow-up. She continued midodrine in the community for 3 weeks with ongoing improvement in her symptoms. Serial chest radiographs (Figs 3B-D) demonstrated regression of the pleural effusions. She remained normotensive and did not experience any other side effects of therapy. The midodrine was then discontinued after 3 weeks. Although 2 weeks later there was some evidence of radiographic deterioration (Fig 3E), this remained stable at her 6-month follow-up (Fig 3F), where she remained symptom free. Disruption or obstruction of the thoracic duct or its tributaries may result in the leakage of chyle into the pleural space. Of chylous effusions, 50% are nontraumatic, with idiopathic chylothorax accounting for 6% of nontraumatic cases.2Doerr C.H. Allen M.S. Nichols III, F.C. Ryu J.H. Etiology of chylothorax in 203 patients.Mayo Clin Proc. 2005; 80: 867-870Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar Although management of nontraumatic chylothorax is centred around treatment of the underlying condition, idiopathic chylothorax presents a unique and complex challenge. Optimal medical and surgical management is essential, centred around dietary therapy (excluding long-chain triglycerides), pleurodesis, and thoracic duct ligation. Several case reports support the use of octreotide, a somatostatin analogue; however, the mechanism of this is poorly understood and it may reduce lymphatic flow by inhibiting gastric, pancreatic, and biliary secretions.3Al-Zubairy S.A. Al-Jazairi A.S. Octreotide as a therapeutic option for management of chylothorax.Ann Pharmacother. 2003; 37: 679-682Crossref PubMed Scopus (54) Google Scholar Several series report the successful use of intravenous etilefrine, an alpha-1 and beta-1 adrenoreceptor agonist, in the management of postoperative chyle leak.4Guillem P. Papachristos I. Peillon C. Triboulet J.P. Etilefrine use in the management of post-operative chyle leaks in thoracic surgery.Interact Cardiovasc Thorac Surg. 2004; 3: 156-160Crossref PubMed Scopus (39) Google Scholar On this basis, Liou et al1Liou D.Z. Warren H. Maher D.P. et al.Midodrine: a novel therapeutic for refractory chylothorax.Chest. 2013; 144: 1055-1057Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar describe the use of midodrine, an oral, selective alpha-1 adrenoreceptor agonist, as a novel therapeutic agent in thoracic duct injury after esophagogastrectomy. Midodrine's relatively low side effect profile and selective alpha-1 agonist properties prompted our trial of this agent in this unique case after appropriate patient consent. Although we acknowledge that the previous pleurodesis attempts with talc and iodine may have had some effect on the chyle leak, the regression on both sides only occurred after adjunctive treatment with midodrine with slight radiographic deterioration after cessation which may suggest a therapeutic effect. Because lymphatic transit through the thoracic duct is closely related to the portal circulation with thoracic duct distension, raised duct pressures, and increased lymph flow rates seen in portal venous hypertension,5Samanta A.K. Saini V.K. Chhuttani P.N. Patra B.S. Vashista S. Datta D.V. Thoracic duct and hepatic lymph in idiopathic portal hypertension.Gut. 1974; 15: 903-906Crossref PubMed Scopus (2) Google Scholar we postulate that modulation of portal blood flow with a potent splanchnic vasoconstrictor such as midodrine6Werling K. Chalasani N. What is the role of midodrine in patients with decompensated cirrhosis?.Gastroenterol Hepatol (N Y). 2011; 7: 134-136PubMed Google Scholar may reduce lymphatic formation and transport. This together with alpha-1 adrenoreceptor-mediated lymphatic constriction7Benoit J.N. Effects of alpha-adrenergic stimuli on mesenteric collecting lymphatics in the rat.Am J Physiol. 1997; 273: R331-R3316PubMed Google Scholar may promote spontaneous resolution of the chyle leak. To our knowledge, this is the first reported case of midodrine therapy in idiopathic chylothorax. It may prove useful as an adjunctive therapy to optimal surgical and medical management, particularly in cases refractory to established therapeutic options, but further work is needed to clarify its potential mechanism of action and efficacy in a wider population in this context. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: P. S. and L.A. have received funding from Carefusion Ltd. for the OPTIMUM Trial (UKCRN 19615) and from Rocket Medical UK for the SINE Study (UKCRN 34053). None declared (P. S., L. A.).