Heart & Lung 44 (2015) 363e365
Contents lists available at ScienceDirect
Heart & Lung journal homepage: www.heartandlung.org
Transudative chylothorax in a patient with liver cirrhosis: A rare association Himanshu Bhardwaj, MD a, *, Bhaskar Bhardwaj, MD b, Ahmed Awab, MD a a Pulmonary Medicine & Critical Care, Internal Medicine, University of Oklahoma Health Sciences Center, P.O. Box 26901, WP1310, Oklahoma City, OK 73190, USA b Internal Medicine, University of Missouri Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 9 March 2015 Received in revised form 13 March 2015 Accepted 13 March 2015 Available online 1 May 2015
Chylothorax is an unusual type of pleural effusion which results from the accumulation of chyle in the pleural cavity. High triglyceride content and presence of chylomicrons in the chyle give this fluid a characteristic milky appearance. Chylothorax most commonly results from the obstruction of the thoracic duct by a malignant lesion or from its traumatic disruption. Liver cirrhosis is an uncommon and frequently underappreciated cause of chylothorax. Pleural effusion in chylothorax is typically described as a lymphocytic predominant, exudative type and it is exceedingly rare to encounter a transudative type of chylothorax. To date, very few cases of transudative chylothoraces have been described in the literature, most commonly in association with liver cirrhosis. Only a limited range of other clinical settings have been linked to transudative chylothorax and timely recognition of these associations can prevent unnecessary, expensive and sometimes invasive workup in this patient population. Ó 2015 Elsevier Inc. All rights reserved.
Keywords: Chylothorax Transudative Chylous effusion Hepatic hydrothorax Liver cirrhosis
Introduction Transudative chylothorax is an exceedingly rare clinical entity which is most commonly seen in the patients of underlying liver cirrhosis.1 The mechanism behind chylothorax formation in liver cirrhosis patients is unclear and is still a matter of ample speculation. Most authors report the translocation of chylous ascitic fluid across the diaphragm as underlying process. Chylous ascites in cirrhotic patients most likely develops secondary to the elevated portal pressures and diffuse degenerative changes in the lymphatics leading to leakage of the chyle into the peritoneal cavity. Case report A 65 year old white male with alcoholic liver cirrhosis was admitted to the hospital with respiratory distress. At the time of admission patient was alert, oriented but in moderate respiratory
Contributions: Manuscript preparation: Himanshu Bhardwaj, MD. Manuscript revision: Bhaskar Bhardwaj, MD. Manuscript review: Ahmed Awab, MD. Sources of financial support: None. Conflict of interest statement: No financial or other potential conflicts of interest exist for any of the author. * Corresponding author. Tel.: þ1 4056268484. E-mail address: [email protected] (H. Bhardwaj). 0147-9563/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2015.03.008
distress. He was afebrile, normotensive with blood pressure at 110/ 70 mm Hg, respiratory rate at 28/min and oxygen saturation at 91% on 2 L/min supplemental oxygen via nasal cannula. On physical examination there were absent breath sounds in most of the left hemithorax and evidence of hepatomegaly with ascites. Chest radiograph showed a large left pleural effusion (Fig. 1). Computed tomographic scan of the chest and abdomen again showed a large left pleural effusion with large ascites (Fig. 2A and B). No abnormal lymphadenopathy or lymphatic obstruction was seen. A bedside ultrasound guided thoracentesis followed by small bore chest tube placement was performed which revealed white milky appearing fluid (Fig. 3). Pleural fluid analysis revealed a lymphocytic predominant transudative type of pleural effusion (Total protein 1.3 g/dl, LDH 53 U/L and cholesterol 16 mg/dl). Further analysis of pleural fluid also showed an elevated level of triglycerides (235 mg/dl) and presence of chylomicrons. A diagnosis of chylothorax was made. Diagnostic paracentesis revealed a high SAAG fluid with triglycerides of 180 mg/dl, consistent with chylous ascites. Patient was made nil-per oral and was placed on total parenteral nutrition (TPN). He was also started on subcutaneous octreotide. After 7 days of therapy, a repeat analysis of pleural fluid taken from the small bore chest tube showed only the presence of transudative effusion without chylothorax consistent with hepatic hydrothorax. Patient was transitioned from TPN to oral reduced fat diet supplemented with medium chain
364
H. Bhardwaj et al. / Heart & Lung 44 (2015) 363e365
Fig. 1. Chest radiograph (anterior-posterior view) showing large left sided pleural effusion.
triglycerides. There was persistent non chylous fluid output from the chest tube; therefore for long-term management of hepatic hydrothorax, a successful talc pleurodesis was performed on the left side (Fig. 4). Patient was discharged home symptom free after total 10 days of hospital stay.
Discussion Chylothorax is a rare type of pleural effusion that results from the accumulation of fluid rich in triglycerides (>110 mg/dl) and chylomicrons in the pleural cavity. High triglyceride levels and chylomicrons give the fluid a characteristic turbid milky appearance. Chylous effusions are typically described as slightly alkaline, exudative and lymphocytic predominant. Most cases of chylothoraces result from a neoplastic obstruction of the thoracic duct, usually lymphomas.2 Liver cirrhosis is considered as a rare and often underappreciated cause of chylothorax. The etiology of chylothorax formation in liver cirrhosis is believed to be related to the translocation of the chylous ascitic fluid via congenital diaphragmatic defects.3 Doerr et al described 16 cases (mostly with underlying liver cirrhosis) of chylothoraces in
association with chylous ascites in their review of total 203 patients of chylothorax.4 Chylous ascites formation in liver cirrhosis patients results from combination of increased portal venous pressure causing elevated thoracic duct lymph flow & pressure; eventually causing rupture of dilated serosal lymphatic vessels.5 This process of chylous ascitic fluid translocation into thoracic cavity can be confirmed by scintigraphy using intraperitoneal injection of radiolabeled technetium (99mTc-Sulfur colloid) followed by demonstration of positive activity in the thorax after 90 min of the injection.3 Chylous pleural effusions are most commonly exudative type on biochemical analysis and it is exceedingly rare to encounter a transudative chylothorax. In one review, Guzman et al described only 13 cases of transudative chylothorax reported in the literature.1 One another review published later reported 10 more cases of transudative type of chylous pleural effusions.5 Agrawal et al also described an additional 7 patients of transudative chylothoraces in their retrospective analysis.6 Based on these reviews, liver cirrhosis represents the most common underlying cause of transudative chylothorax. Other less common etiologies include: nephrotic syndrome, amyloidosis, superior vena cava thrombosis, congestive heart failure and sclerosing mesentritis.7,8 Management of cirrhosis related chylothorax is mostly conservative. Intermittent thoracentesis for symptomatic relief of the dyspnea constitutes the initial approach for slowly accumulating chylous effusions. Use of the tunneled indwelling pleural catheters (TIPCs) in the management of chylothoraces is theoretically contraindicated due to the risk of significant lymphocyte, protein, fat and immunoglobulin loss in the chyle. However some authors have recently reported successful utilization of TIPCs for both benign as well as malignant chylothoraces without significant complications.9,10 While there may be a role of TIPCs in the management of chylothoraces, at this stage their use should be considered experimental only pending more prospective studies. For rapidly accumulating chylothorax, a more aggressive approach of instituting complete bowel rest using total parenteral nutrition supported by somatostatin analogue octreotide is preferred. Total parenteral nutrition is later transitioned to low fat oral diet supplemented with medium chain triglycerides which are absorbed directly by the intestinal cells thus bypassing the thoracic duct. Octreotide, a synthetic somatostatin analogue is thought to reduce the lymph flow and fluid volume in the thoracic duct by decreasing overall gastrointestinal tract absorption and secretion. Current use of octreotide in the management of chylothoraces in adult
Fig. 2. A) CT-Scan abdomen showing large ascites (arrows). B) CT-scan chest showing large left pleural effusion (arrow).
H. Bhardwaj et al. / Heart & Lung 44 (2015) 363e365
365
Fig. 3. Chest tube drainage chamber showing milky appearing pleural fluid consistent with underlying chylothorax.
Fig. 4. Post pleurodesis chest radiograph (anterior-posterior view) showing clear left hemithorax, small bore pigtail catheter can still be seen in place in the pleural cavity.
population is based on case reports & case series only and is considered experimental.11 For patients not responding to these conservative measures, chemical pleurodesis using talc can be tried. The success of chemical pleurodesis generally depends on adequate drainage of the pleural space prior to the instillation of the talc. Due to rapid movement of fluid from abdominal cavity into thoracic cavity in the settings of underlying hepatic hydrothorax, pleurodesis is extremely difficult and is rarely successful. More recently, successful use of transjugular intrahepatic portosystemic shunt (TIPS) has also been described in the management of cirrhosis related chylothorax and chylous ascites.12,13 TIPS may be a better option than chemical pleurodesis in this patient group but more studies are needed in this area before any conclusion. In summary, above case represents a seemingly underappreciated and rare transudative type chylothorax in a cirrhotic patient. As pleural effusions in liver cirrhosis patients do not always require a diagnostic thoracentesis and triglyceride level measurement in the pleural fluid is often not checked which may explain the lower reported frequency of chylothorax in this patient population.3 Clinicians should be aware of this rare clinical entity as differential diagnoses in the context of transudative chylothorax are limited. Familiarity with this clinical association can avoid unnecessary expensive and sometime invasive workups.
References 1. Diaz-Guzman E, Culver DA, Stoller JK. Transudative chylothorax: report of two cases and review of the literature. Lung. 2005;183(3):169e175. 2. Valentine VG, Raffin TA. The management of chylothorax. Chest. 1992;102: 586591. 3. Romero S, Martín C, Hernandez L, et al. Chylothorax in cirrhosis of the liver: analysis of its frequency and clinical characteristics. Chest. 1998;114:154e159. 4. Doerr CH, Allen MS, Nichols 3rd FC, et al. Etiology of chylothorax in 203 patients. Mayo Clin Proc. 2005;80(7):867e870. 5. Cárdenas A, Chopra S. Chylous ascites. Am J Gastroenterol. 2002;97:1896e1900. 6. Agrawal V, Doelken P, Sahn SA. Pleural fluid analysis in chylous pleural effusion. Chest. 2008;133(6):1436e1441. 7. Maldonado F, Hawkins FJ, Daniels CE, et al. Pleural fluid characteristics of chylothorax. Mayo Clin Proc. 2009;84(2):129e133. 8. Rice BL, Stoller JK, Heresi GA. Transudative chylothorax associated with sclerosing mesenteritis. Respir Care. 2010;55(4):475e477. 9. DePew ZS, Iqbal S, Mullon JJ, et al. The role for tunneled indwelling pleural catheters in patients with persistent benign chylothorax. Am J Med Sci. 2013 Nov;346(5):349e352. 10. Jimenez CA, Mhatre AD, Martinez CH, et al. Use of an indwelling pleural catheter for the management of recurrent chylothorax in patients with cancer. Chest. 2007;132(5):1584e1590. 11. Kalomenidis I. Octreotide and chylothorax. Curr Opin Pulm Med. 2006;12(4): 264e267. 12. Kikolski SG, Aryafar H, Rose SC, et al. Transjugular intrahepatic portosystemic shunt for treatment of cirrhosis-related chylothorax and chylous ascites: single-institution retrospective experience. Cardiovasc Intervent Radiol. 2013;36(4):992e997. 13. Kinney TB, Ferrara SL, Miller FJ, et al. Transjugular intrahepatic portosystemic shunt creation as treatment for refractory chylous ascites and chylothorax in a patient with cirrhosis. J Vasc Interv Radiol. 2004;15:85.
Contents lists available at ScienceDirect
Heart & Lung journal homepage: www.heartandlung.org
Transudative chylothorax in a patient with liver cirrhosis: A rare association Himanshu Bhardwaj, MD a, *, Bhaskar Bhardwaj, MD b, Ahmed Awab, MD a a Pulmonary Medicine & Critical Care, Internal Medicine, University of Oklahoma Health Sciences Center, P.O. Box 26901, WP1310, Oklahoma City, OK 73190, USA b Internal Medicine, University of Missouri Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 9 March 2015 Received in revised form 13 March 2015 Accepted 13 March 2015 Available online 1 May 2015
Chylothorax is an unusual type of pleural effusion which results from the accumulation of chyle in the pleural cavity. High triglyceride content and presence of chylomicrons in the chyle give this fluid a characteristic milky appearance. Chylothorax most commonly results from the obstruction of the thoracic duct by a malignant lesion or from its traumatic disruption. Liver cirrhosis is an uncommon and frequently underappreciated cause of chylothorax. Pleural effusion in chylothorax is typically described as a lymphocytic predominant, exudative type and it is exceedingly rare to encounter a transudative type of chylothorax. To date, very few cases of transudative chylothoraces have been described in the literature, most commonly in association with liver cirrhosis. Only a limited range of other clinical settings have been linked to transudative chylothorax and timely recognition of these associations can prevent unnecessary, expensive and sometimes invasive workup in this patient population. Ó 2015 Elsevier Inc. All rights reserved.
Keywords: Chylothorax Transudative Chylous effusion Hepatic hydrothorax Liver cirrhosis
Introduction Transudative chylothorax is an exceedingly rare clinical entity which is most commonly seen in the patients of underlying liver cirrhosis.1 The mechanism behind chylothorax formation in liver cirrhosis patients is unclear and is still a matter of ample speculation. Most authors report the translocation of chylous ascitic fluid across the diaphragm as underlying process. Chylous ascites in cirrhotic patients most likely develops secondary to the elevated portal pressures and diffuse degenerative changes in the lymphatics leading to leakage of the chyle into the peritoneal cavity. Case report A 65 year old white male with alcoholic liver cirrhosis was admitted to the hospital with respiratory distress. At the time of admission patient was alert, oriented but in moderate respiratory
Contributions: Manuscript preparation: Himanshu Bhardwaj, MD. Manuscript revision: Bhaskar Bhardwaj, MD. Manuscript review: Ahmed Awab, MD. Sources of financial support: None. Conflict of interest statement: No financial or other potential conflicts of interest exist for any of the author. * Corresponding author. Tel.: þ1 4056268484. E-mail address: [email protected] (H. Bhardwaj). 0147-9563/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2015.03.008
distress. He was afebrile, normotensive with blood pressure at 110/ 70 mm Hg, respiratory rate at 28/min and oxygen saturation at 91% on 2 L/min supplemental oxygen via nasal cannula. On physical examination there were absent breath sounds in most of the left hemithorax and evidence of hepatomegaly with ascites. Chest radiograph showed a large left pleural effusion (Fig. 1). Computed tomographic scan of the chest and abdomen again showed a large left pleural effusion with large ascites (Fig. 2A and B). No abnormal lymphadenopathy or lymphatic obstruction was seen. A bedside ultrasound guided thoracentesis followed by small bore chest tube placement was performed which revealed white milky appearing fluid (Fig. 3). Pleural fluid analysis revealed a lymphocytic predominant transudative type of pleural effusion (Total protein 1.3 g/dl, LDH 53 U/L and cholesterol 16 mg/dl). Further analysis of pleural fluid also showed an elevated level of triglycerides (235 mg/dl) and presence of chylomicrons. A diagnosis of chylothorax was made. Diagnostic paracentesis revealed a high SAAG fluid with triglycerides of 180 mg/dl, consistent with chylous ascites. Patient was made nil-per oral and was placed on total parenteral nutrition (TPN). He was also started on subcutaneous octreotide. After 7 days of therapy, a repeat analysis of pleural fluid taken from the small bore chest tube showed only the presence of transudative effusion without chylothorax consistent with hepatic hydrothorax. Patient was transitioned from TPN to oral reduced fat diet supplemented with medium chain
364
H. Bhardwaj et al. / Heart & Lung 44 (2015) 363e365
Fig. 1. Chest radiograph (anterior-posterior view) showing large left sided pleural effusion.
triglycerides. There was persistent non chylous fluid output from the chest tube; therefore for long-term management of hepatic hydrothorax, a successful talc pleurodesis was performed on the left side (Fig. 4). Patient was discharged home symptom free after total 10 days of hospital stay.
Discussion Chylothorax is a rare type of pleural effusion that results from the accumulation of fluid rich in triglycerides (>110 mg/dl) and chylomicrons in the pleural cavity. High triglyceride levels and chylomicrons give the fluid a characteristic turbid milky appearance. Chylous effusions are typically described as slightly alkaline, exudative and lymphocytic predominant. Most cases of chylothoraces result from a neoplastic obstruction of the thoracic duct, usually lymphomas.2 Liver cirrhosis is considered as a rare and often underappreciated cause of chylothorax. The etiology of chylothorax formation in liver cirrhosis is believed to be related to the translocation of the chylous ascitic fluid via congenital diaphragmatic defects.3 Doerr et al described 16 cases (mostly with underlying liver cirrhosis) of chylothoraces in
association with chylous ascites in their review of total 203 patients of chylothorax.4 Chylous ascites formation in liver cirrhosis patients results from combination of increased portal venous pressure causing elevated thoracic duct lymph flow & pressure; eventually causing rupture of dilated serosal lymphatic vessels.5 This process of chylous ascitic fluid translocation into thoracic cavity can be confirmed by scintigraphy using intraperitoneal injection of radiolabeled technetium (99mTc-Sulfur colloid) followed by demonstration of positive activity in the thorax after 90 min of the injection.3 Chylous pleural effusions are most commonly exudative type on biochemical analysis and it is exceedingly rare to encounter a transudative chylothorax. In one review, Guzman et al described only 13 cases of transudative chylothorax reported in the literature.1 One another review published later reported 10 more cases of transudative type of chylous pleural effusions.5 Agrawal et al also described an additional 7 patients of transudative chylothoraces in their retrospective analysis.6 Based on these reviews, liver cirrhosis represents the most common underlying cause of transudative chylothorax. Other less common etiologies include: nephrotic syndrome, amyloidosis, superior vena cava thrombosis, congestive heart failure and sclerosing mesentritis.7,8 Management of cirrhosis related chylothorax is mostly conservative. Intermittent thoracentesis for symptomatic relief of the dyspnea constitutes the initial approach for slowly accumulating chylous effusions. Use of the tunneled indwelling pleural catheters (TIPCs) in the management of chylothoraces is theoretically contraindicated due to the risk of significant lymphocyte, protein, fat and immunoglobulin loss in the chyle. However some authors have recently reported successful utilization of TIPCs for both benign as well as malignant chylothoraces without significant complications.9,10 While there may be a role of TIPCs in the management of chylothoraces, at this stage their use should be considered experimental only pending more prospective studies. For rapidly accumulating chylothorax, a more aggressive approach of instituting complete bowel rest using total parenteral nutrition supported by somatostatin analogue octreotide is preferred. Total parenteral nutrition is later transitioned to low fat oral diet supplemented with medium chain triglycerides which are absorbed directly by the intestinal cells thus bypassing the thoracic duct. Octreotide, a synthetic somatostatin analogue is thought to reduce the lymph flow and fluid volume in the thoracic duct by decreasing overall gastrointestinal tract absorption and secretion. Current use of octreotide in the management of chylothoraces in adult
Fig. 2. A) CT-Scan abdomen showing large ascites (arrows). B) CT-scan chest showing large left pleural effusion (arrow).
H. Bhardwaj et al. / Heart & Lung 44 (2015) 363e365
365
Fig. 3. Chest tube drainage chamber showing milky appearing pleural fluid consistent with underlying chylothorax.
Fig. 4. Post pleurodesis chest radiograph (anterior-posterior view) showing clear left hemithorax, small bore pigtail catheter can still be seen in place in the pleural cavity.
population is based on case reports & case series only and is considered experimental.11 For patients not responding to these conservative measures, chemical pleurodesis using talc can be tried. The success of chemical pleurodesis generally depends on adequate drainage of the pleural space prior to the instillation of the talc. Due to rapid movement of fluid from abdominal cavity into thoracic cavity in the settings of underlying hepatic hydrothorax, pleurodesis is extremely difficult and is rarely successful. More recently, successful use of transjugular intrahepatic portosystemic shunt (TIPS) has also been described in the management of cirrhosis related chylothorax and chylous ascites.12,13 TIPS may be a better option than chemical pleurodesis in this patient group but more studies are needed in this area before any conclusion. In summary, above case represents a seemingly underappreciated and rare transudative type chylothorax in a cirrhotic patient. As pleural effusions in liver cirrhosis patients do not always require a diagnostic thoracentesis and triglyceride level measurement in the pleural fluid is often not checked which may explain the lower reported frequency of chylothorax in this patient population.3 Clinicians should be aware of this rare clinical entity as differential diagnoses in the context of transudative chylothorax are limited. Familiarity with this clinical association can avoid unnecessary expensive and sometime invasive workups.
References 1. Diaz-Guzman E, Culver DA, Stoller JK. Transudative chylothorax: report of two cases and review of the literature. Lung. 2005;183(3):169e175. 2. Valentine VG, Raffin TA. The management of chylothorax. Chest. 1992;102: 586591. 3. Romero S, Martín C, Hernandez L, et al. Chylothorax in cirrhosis of the liver: analysis of its frequency and clinical characteristics. Chest. 1998;114:154e159. 4. Doerr CH, Allen MS, Nichols 3rd FC, et al. Etiology of chylothorax in 203 patients. Mayo Clin Proc. 2005;80(7):867e870. 5. Cárdenas A, Chopra S. Chylous ascites. Am J Gastroenterol. 2002;97:1896e1900. 6. Agrawal V, Doelken P, Sahn SA. Pleural fluid analysis in chylous pleural effusion. Chest. 2008;133(6):1436e1441. 7. Maldonado F, Hawkins FJ, Daniels CE, et al. Pleural fluid characteristics of chylothorax. Mayo Clin Proc. 2009;84(2):129e133. 8. Rice BL, Stoller JK, Heresi GA. Transudative chylothorax associated with sclerosing mesenteritis. Respir Care. 2010;55(4):475e477. 9. DePew ZS, Iqbal S, Mullon JJ, et al. The role for tunneled indwelling pleural catheters in patients with persistent benign chylothorax. Am J Med Sci. 2013 Nov;346(5):349e352. 10. Jimenez CA, Mhatre AD, Martinez CH, et al. Use of an indwelling pleural catheter for the management of recurrent chylothorax in patients with cancer. Chest. 2007;132(5):1584e1590. 11. Kalomenidis I. Octreotide and chylothorax. Curr Opin Pulm Med. 2006;12(4): 264e267. 12. Kikolski SG, Aryafar H, Rose SC, et al. Transjugular intrahepatic portosystemic shunt for treatment of cirrhosis-related chylothorax and chylous ascites: single-institution retrospective experience. Cardiovasc Intervent Radiol. 2013;36(4):992e997. 13. Kinney TB, Ferrara SL, Miller FJ, et al. Transjugular intrahepatic portosystemic shunt creation as treatment for refractory chylous ascites and chylothorax in a patient with cirrhosis. J Vasc Interv Radiol. 2004;15:85.
