Management of chylothorax

INTRODUCTION — Chylothorax is the accumulation of chyle in the pleural space. Chylothorax can be due to many etiologies, which are classified as nontraumatic (usually the result of malignancy, congenital conditions, or infection) and traumatic (usually the result of surgery or nonsurgical trauma). (table 1). Chylothorax is associated with significant morbidity and mortality if left untreated.

The management of chylothorax will be reviewed here. The etiology, clinical presentation, and diagnosis of chylothorax are discussed separately. (See "Etiology, clinical presentation, and diagnosis of chylothorax".)

GENERAL PRINCIPLES — No management algorithm has been universally adopted for patients with chylothorax since multiple clinical factors unique to each patient impact therapy including etiology (table 1), symptoms, age, functional status, local expertise, and rate of chyle accumulation. There are no well-conducted randomized trials comparing therapies to inform management decisions for chyle leaks after esophageal resection, which is the most common postoperative setting for chylothorax [1]. Therefore, our approach is based upon clinical experience and data that are mostly derived from case series and nonrandomized observational comparative studies of patients with postoperative chyle leak. There are few high-quality studies.

Low-output chylothorax — Patients are considered to have low-output chylothorax if the estimated or known volume of drainage or accumulation is less than 1 L chyle per day [1,2]. Many patients with medical reasons for their chylothorax and postoperative patients with chyle leaks due to minor trauma to the main thoracic duct or disruptions of thoracic duct tributaries fall into this category. In general, these patients benefit from a staged care plan that moves from least invasive options to more invasive interventions during several days to weeks of observation. This includes:

●Drainage for symptom control, dietary control measures, and treatment of the underlying condition (table 1). Adjuncts (somatostatin/octreotide) are often also administered to in this population. As a general rule of thumb, the larger the leak and the higher likelihood of injury to the main thoracic duct rather than a lymphatic tributary, the more likely a patient will fail such conservative therapies, increasing the need for a definitive intervention. (See 'Medical care for those not requiring immediate intervention' below.)

●Should these measures fail, then chemical or surgical pleurodesis, percutaneous thoracic duct embolization (TDE), disruption or sclerosis by lymphangiography with highly viscous poppy-seed oil (Lipiodol, ethiodized oil), surgical thoracic duct ligation or repair by thoracotomy or thoracoscopy, ligation of lymphatic tributaries to the thoracic duct, or some combination thereof all options is suggested. (See 'Patients who fail medical therapy' below.)

●Older patients and patients with poor functional reserve may benefit from early implementation of minimally invasive procedures to decrease chyle leakage, such as lymphatic duct embolization or lymphangiography with Lipiodol, because they may tolerate poorly dietary restrictions and limitations to early ambulation attendant to prolonged conservative therapy.

High-output chylothorax — High-output chylothorax (estimated or known volume >1 L chyle per day) is most commonly seen in postsurgical patients (especially esophagectomy) and those with liver cirrhosis [1-3]. In such patients, early interventions (eg, surgical thoracic duct ligation, surgical ligation or clipping of thoracic duct tributaries, percutaneous TDE, or lymphangiography with Lipiodol) are typically needed early (often within the first few days after diagnosis) since conservative strategies are more likely to fail in this population. (See 'Patients who fail medical therapy' below.)

MANAGEMENT OF POSTOPERATIVE CHYLE LEAKS — Postoperative chyle leaks are the most common form of chylothorax encountered. While most postoperative leaks are low volume (<1 L per day), some are high volume (>1 L per day), with the former being treated conservatively and the latter typically treated aggressively with surgical interventions or percutaneous embolization after a few days of observation.

Of note, prophylactic thoracic duct ligation during surgery for intrathoracic cancer that presents an increased risk for chylothorax, such as esophagectomy, has not been demonstrated to prevent postoperative chylothorax and may reduce survival possibly due to decreased recirculation of proteins and immune factors between lymph and the bloodstream [4]. Conversely, thoracic duct ligation performed after the occurrence of chylothorax in patients after initial esophagectomy has not been shown to impact postoperative complications or long-term survival [5].

Evaluation for early intervention (high output) — Patients in the postoperative setting are at greatest risk of having high-volume chyle leaks (>1 L per day) that require intervention (hours to a few days). In such cases, a chest tube is typically already in place (eg, after thoracic or esophageal surgery) while in others a chest tube may have been placed to drain a postoperative pleural effusion (eg, after neck or spinal surgery). The mortality is high in this population such that aggressive intervention is warranted.

In most cases, patients with high-volume leaks are treated with complete bowel rest by the administration of parenteral nutrition, aggressive correction of fluid and electrolyte losses, ligation of the thoracic duct, or percutaneous thoracic duct embolization (TDE; within hours to days). Some surgeons initiate surgical interventions immediately for high-output chylothorax after esophagectomy because of a considerable probability that the main thoracic duct was disrupted but observe patients with conservative therapy for several days after other types of surgery [3].

Initial treatment with low-fat oral diets provides no benefit for postoperative high-output chyle leaks, although an oral diet with medium-chain triglycerides may provide transitional nutrition for patients who experience decreased chyle drainage (<500 mL/day) after initial treatment with parenteral nutrition and bowel rest [3].

While waiting for surgery to manage the chylothorax, some patients may benefit from somatostatin/octreotide, although these drugs are seldom if ever sufficient to resolve a high-output chyle leak after surgery if the main thoracic duct was damaged, as usually occurs with esophagectomy.

Patients who experience chylothorax after pulmonary resection, however, usually have lymphatic disruption involving small collaterals within the base of the mediastinal N2 lymph nodes [3]. These patients may respond to 48 hours of nonoperative therapies. It should be noted, however, that high-output chyle drainage >1 L/day is rare after lobectomy and mediastinal lymph node dissections [3].

The rationale for an initial aggressive approach to managing high-output chylothorax is that these patients may have major thoracic duct injury, which is unlikely to close spontaneously rather than leaks that originate from smaller thoracic duct tributary, which are more likely to undergo spontaneous closure. In addition, early intervention accelerates ambulation and avoids severe metabolic or nutritional derangements that are more likely to occur in those with large amounts of chyle loss. (See 'Pleural drainage to control symptoms' below and 'Dietary modification' below and 'Somatostatin and octreotide' below and 'Thoracic duct ligation' below.)

The timing of intervention varies. While some experts perform immediate intervention in those who drain >1 L of chyle in the first postoperative day [6], other experts may observe for a period and intervene in those who continue to drain >1 L for up to three to five consecutive days despite conservative therapy [7]. In this setting, interventions such as percutaneous TDE or thoracic duct ligation or fibrin glue repair by thoracotomy or thoracoscopy are likely to be successful and may be combined with pleurodesis if thoracotomy or thoracoscopy are performed [8,9].

Percutaneous techniques such as TDE/thoracic duct disruption or therapeutic lymphangiography with Lipiodol have gained increased support as initial interventional management. Some centers with extensive experience with percutaneous lymphatic interventions may opt for these procedures before performing surgery, an approach that is rapidly becoming standard initial therapy [1,10,11]. (See 'Percutaneous or retrograde lymphatic embolization or disruption' below.)

Patients not in need of early intervention (low output) — In postoperative patients with a low-volume leak or a high-volume leak that responds dramatically to conservative therapy, a management strategy that is similar to that performed in nonsurgical cases of chylothorax is appropriate (ie, with continued drainage of chyle, somatostatin/octreotide, and dietary modification, generally with parenteral nutrition) (see 'Medical care for those not requiring immediate intervention' below). Intervention is considered for those who fail these conservative measures (eg, surgical or percutaneous intervention). (See 'Thoracic duct ligation' below and 'Percutaneous or retrograde lymphatic embolization or disruption' below.)

After pulmonary resection and mediastinal lymph node dissection for lung cancer, some experts recommend early reoperation if chyle drainage is >450 to 500 mL/day [12,13], although few data support this approach. Observational studies indicate that conservative therapy with a low-fat diet with or without octreotide resolved the chylothorax in most of these patients if they respond to conservative therapy within the first three days [3,14].

Postpneumonectomy chylothorax — Patients with a chylothorax in a postpneumonectomy space in the early postoperative period are treated a little differently. Rapid postoperative filling of the pneumonectomy space with fluid (which otherwise takes one to four weeks) typically should raise the suspicion for chylothorax. If confirmed by thoracentesis (patients rarely have chest tubes in place after pneumonectomy) and no tension is present, chylothorax is managed with dietary control measures (ie, fasting and total parenteral nutrition) without chest tube drainage and patients should immediately be evaluated for an intervention. If there is evidence of mediastinal shift to the contralateral side, patients should have an emergency chest tube placed and also be evaluated for immediate intervention to gain control of the lymphatic leak [15,16]. One case report described a patient with chylothorax and mediastinal shift after pneumonectomy that responded with chest tube drainage and a period of parenteral nutritional support [17], although most clinicians do not adopt this strategy.

The rationale for not placing a chest tube for drainage in those without evidence of mediastinal shift is the depletion of nutrients, immunoglobulins, and lymphocytes as well as that the placement of a chest tube will further reduce pressure in an already low pressure postpneumonectomy space; the latter potentially worsens the leak by promoting flow from the thoracic duct (high pressure) to the pleural space (low pressure), thereby prohibiting spontaneous healing. By comparison, in patients who have a lobectomy, expansion of the remaining lung with or without a chest tube in place helps to raise the pleural pressure and provide some "tamponade effect" on the leaking duct.

MEDICAL CARE FOR THOSE NOT REQUIRING IMMEDIATE INTERVENTION

Initial therapies — Most patients with chylothorax who do not require urgent invasive interventions should undergo pleural drainage if needed for symptom control and dietary modification while the underlying disorder is being addressed (table 1) [3,12,18]. This strategy reduces the rate of accumulation in many patients and in some cases allows the opportunity for cases due to chyle leak to heal spontaneously without surgical intervention.

Pleural drainage to control symptoms — If a chest tube is not already in place, most patients should undergo drainage of chyle with a chest tube or indwelling catheter (without suction) as an initial form of therapy to relieve symptoms (typically dyspnea) due to the effusion, although in some nonsurgical patients intermittent thoracentesis is sufficient. A chest tube or catheter left in place helps inform the clinician regarding the volume of chyle loss per day which impacts future decisions regarding therapy (eg, type and timing of interventional or surgical modality). However, there are some exceptions to the rule where drainage is not typically performed:

●Asymptomatic nonsurgical patients with small effusions – After an initial diagnostic thoracentesis to diagnose a chylothorax, repeat thoracentesis or catheter drainage is not necessary in this population, but patients may benefit from dietary measures, treatment of the underlying condition, and serial observation.

●Patients with chylous ascites. (See 'Chylous ascites' below.)

●Postpneumonectomy patients with a chylothorax in the early postoperative course who do not have evidence of mediastinal shift. (See 'Postpneumonectomy chylothorax' above.)

In general, the decision to proceed with continued drainage or intermittent thoracentesis is dependent upon the rate of estimated loss of chyle/rate of re-accumulation as well as nutritional status, age, functional status, patient prognosis, and patient preference. While there are no guidelines to facilitate this decision, we generally use the following principles:

●With the exception of postpneumonectomy patients (see 'Postpneumonectomy chylothorax' above), most surgical patients who develop a postoperative chylothorax, continued drainage is typically necessary, particularly those who have chyle loss on the higher side (eg, 500 to 1000 mL per day). For nonsurgical patients with chylothoraces that rapidly re-accumulate after a diagnostic thoracentesis (hours to days), continuous chest tube or catheter drainage is generally needed to relieve symptoms.

●For all patients with chylothorax, long-term, continuous chest tube drainage is associated with immunosuppression from loss of protein, lymphocytes, and immunoglobulins [19,20]. Thus, continuous pleural fluid drainage is generally limited to less than 14 days to minimize the risk of infection, malnutrition, and electrolyte losses as well as diminish tolerance for definitive surgery if later required. The duration of drainage may need to be shortened for older patients and those with poor functional status to avoid delaying ambulation. For patients with postoperative chylothorax, intervention (eg, thoracic duct ligation or embolization) is generally indicated sooner (eg, within three to five days) if the drainage of pleural fluid exceeds 1 to 1.5 L/day, or if the drainage of chyle results in weight loss and/or progressive hypoproteinemia despite aggressive nutritional therapy [21,22]. (See 'Evaluation for early intervention (high output)' above.)

●For patients who have a gradual reaccumulation of chyle (eg, outpatients with nonsurgical or nontraumatic chylothorax who reaccumulate over days to weeks or have <50 mL chyle output per day), intermittent therapeutic thoracentesis (eg, every two to six weeks or longer) or use of an indwelling catheter for home drainage (eg, drainage every week) is appropriate. (See "Ultrasound-guided thoracentesis" and "Management of malignant pleural effusions", section on 'Indwelling pleural catheter (IPC)'.)

All patients managed with continuous drainage of chylous pleural fluid require monitoring of serum electrolytes, lymphocyte counts, albumin, total protein, and weight. For those with high-volume loss, patients may require blood tests two to three times a week until they maintain stable values while those with lower rates of loss may have testing every few weeks. Patients who undergo continuous drainage with restricted oral diet require careful attention to nutritional needs with provision of enteral or parenteral nutrients designed to offset the protein and calorie losses related to drainage of the chylothorax. Consultation with a nutritionist is advised. (See 'Dietary modification' below.)

Dietary modification — The principles of dietary management focus on reducing the flow of chyle through the thoracic duct by either of the following:

●Oral or enteral low-fat diet – Patients suitable for an oral or enteral diet are those with low-volume chylothorax due to any etiology. Patients should be assessed by a dietician and given clear instructions on eating a high-protein, low-fat (<10 g fat/day) diet. Since decreasing fat intake decreases fat absorption from the gut and therefore decreases the flow of chyle, this should reduce the accumulation of chyle in the pleural space [8,23]. Dietary exclusion of long-chain triglycerols (LCTs) is encouraged; this avoids their conversion into monoglycerides and free fatty acids (FFA), which are transported as chylomicrons to the intestinal lymph ducts. An oral diet is always preferred to an enteral diet, when possible. Some clinicians provide a fat-free diet (<5 kcal fat/serving) initially but such diets are highly unpalatable and difficult to tolerate for more than a few days. General principles include the following:

•Initially, patients should receive a low-fat, high-protein diet with an emphasis on reducing LCTs.

•Oral vitamins should be provided, although decreased absorption of fat-soluble vitamins with low-fat diets may require parenteral supplementation of these micronutrients.

•Peripheral intravenous (IV) fat emulsions (250 mL of 20 percent emulsion IV three times a week) may be appropriate if it is felt that the patient is at high risk of essential fatty acid deficiency.

•Enteral nutrition may be prescribed as a supplement to oral nutrition or as the sole source of nutrition for patients who can take nothing by mouth.

•If pleural drainage decreases, medium chain triglycerols (MCTs) can be introduced orally as a liquid or capsule or in the form of enteral feeding products, which may not be tolerated because of taste. MCTs are absorbed directly into intestinal cells and transported directly to the liver via the portal vein, thus bypassing the thoracic duct [12]. Common adverse effects are gastrointestinal upset, steatorrhea, and elevated cholesterol blood levels. (See "Chylous, bloody, and pancreatic ascites", section on 'Management'.)

•Fat intake is gradually increased as the patient improves and the volume of pleural drainage decreases. Because each patient responds differently to dietary modification, no specific regimen is available to time liberalization of fat intake. Nonetheless, we typically utilize a low-fat diet for 7 to 10 days. If patients continue to improve with decreased pleural fluid drainage, LCTs are added to the diet with progression to an unrestricted diet as tolerated [23]. If patients do not improve, then total parenteral nutrition (TPN) is appropriate.

●Total parenteral nutrition – For patients with high-volume chyle leaks (eg, postoperative leaks >1 L/day), the administration of TPN is generally preferred since a dramatic reduction in the flow of chyle may promote healing and prevent acute nutritional deficiencies [24]. TPN may also be administered to patients who are unable to be fed orally or enterally and those in whom oral and enteral dietary measures fail. No fat restrictions for TPN apply since lipids are administered intravenously. (See "Nutrition support in intubated critically ill adult patients: Parenteral nutrition".)

Treatment of the underlying condition — A critical step in the management chylothorax is treatment of the underlying disease (table 1) [9,25,26]. For example, patients with chylothorax due to underlying sarcoidosis may respond to glucocorticoid therapy, and those due to infection may respond to treatment with antimicrobials.

Adjunctive therapies

Somatostatin and octreotide — Somatostatin or octreotide, a somatostatin analogue that has a longer half-life in the circulation, can be used as adjunctive therapies. They are commonly used routinely in conjunction with chest tube drainage and bowel rest with TPN in postoperative patients with chyle leaks (<1 L per day), since this regimen has been shown to increase the probability of avoiding surgical repair [27]. In medical patients with chylothorax due to nonsurgical etiologies (eg, cancer) some experts choose to use them in conjunction with conservative therapy while others only administer somatostatin/octreotide when conservative measures have failed or have been partially successful, or when thoracic duct surgery or embolization is not feasible. Their use should be limited to a trial of a few weeks. (See 'Less well-established options' below.)

Somatostatin and octreotide decrease the volume of fluid within the thoracic duct by inhibiting gastric, pancreatic, and biliary secretions, and inhibiting absorption of chyle from the intestine [28,29]. Because of the reduction in chyle production and flow rate, these agents have been successfully used in case reports and case series to treat spontaneous chylothorax, congenital chylothorax, postoperative chylothorax, and chylothorax due to malignancy and yellow nail syndrome, often in combination with a reduced fat diet supplemented with medium chain triglycerides [3,27,30-33].

●One systematic review of octreotide for management of chylothorax after cardiothoracic surgery noted benefit in patients with moderate to large volume chylothorax when used as adjunctive therapy with TPN and bowel rest noting benefit within two to three days [27]. (See "Physiology of somatostatin and its analogues".)

●A small case series (seven patients) and isolated case reports have described successful management of malignant chylothorax using subcutaneous octreotide and a fat-free diet [31,32].

Reported doses of somatostatin and octreotide for treatment of chylothorax vary and the optimal dose and route of administration are not known. In a series of adult patients, somatostatin was given by intravenous infusion 6 mg/day for two weeks or by subcutaneous injection, 50 micrograms every eight hours; octreotide was given in subcutaneous doses of 50 to 200 micrograms every eight hours for 2 to 14 days [3,28].

In general, side effects of somatostatin and octreotide include cutaneous flushing, nausea, diarrhea, sinus bradycardia, injection site pain, transient hypothyroidism, and elevated liver function tests. Prophylactic administration of octreotide before lobectomy for lung cancer does not appear to prevent postoperative chylothorax [34].

Midodrine — Two case reports suggested that midodrine, an alpha 1-adrenergic agonist that causes vasoconstriction of the lymph system, reduced drainage in a patient with postoperative, high-output chylothorax and a patient with idiopathic chylothorax, both of whom failed to respond to dietary modifications and surgical intervention [35,36]. A similar case report of success with another alpha adrenergic agonist, etilefrine, has also been described [37].

Monitoring the response — The response to conservative therapy should be monitored clinically by measuring the volume of daily drainage for those with a chest tube or catheter in place. Periodic imaging, with chest radiograph or chest computed tomography, may also provide information regarding rate of reaccumulation for those with slowly accumulating fluid who do not have a chest tube in place.

Duration of monitoring — The duration of monitoring the response to conservative therapy before resorting to definitive measures remains controversial and is mostly derived from the experience with patients who have postsurgical chylothorax [24,38] since the timing for resolution is variable. While some leaks take a few days to respond, others may take longer (two weeks or more). The decision regarding when to intervene with definitive measures varies in surgical and non-surgical settings:

●In the postoperative setting, early intervention within one to five days is indicated in those in whom fluid output exceeds 1 L/day or when severe metabolic or nutrition derangements occur [6,9,39] (see 'Evaluation for early intervention (high output)' above). In those with chyle leaks <1 L per day, intervention is typically warranted if a chylothorax does not respond to conservative measures by about two weeks. Optimal timing of interventions, however, remain unclear because of the paucity of high-quality studies to guide decisions [1].

●In the non-surgical patient, timing of interventions is based upon multiple factors. These include initial rate of pleural drainage, the underlying disease, the severity of respiratory compromise due to the chylothorax, the ability to drain the pleural space adequately, and the degree of response to conservative measures. For example, a declining output at two weeks in response to conservative therapies in a patient with chylothorax should encourage the clinician to persist with such measures while no response or a plateaued response may be an indication to consider an interventional or surgical procedure.

Efficacy — A large proportion of patients improve with conservative therapies, but success rates vary and are wide ranging. Success depends upon factors including etiology (table 1), reversibility in response to etiology-specific therapies, and volume of pleural fluid drainage. In general, patients who drain more than 1 L/day are unlikely to respond to conservative therapy and usually require surgical intervention within five days or less [6]. By contrast, in patients with less than 500 mL of chest tube drainage in the first 24 hours after cessation of oral intake and initiation of TPN, the chylothorax tends to resolve with conservative management [3,12]. Case series report the following success rates:

●Conservative measures have a 50 to 80 percent success rate in postoperative chylothorax [3,6,8,12,14,18], with higher success rates reported in patients with <500 mL/day pleural fluid drainage and lower in those with volumes >1 L per day [6,12]. Conservative measures are also successful in approximately 50 percent of patients with nonsurgical traumatic chylothorax [8].

●In patients with benign disease such as infection or sarcoidosis, conservative measures are successful in approximately 40 to 80 percent [8].

●Treatment of the underlying malignancy with first line therapies including chemotherapy and irradiation has also been successful [9,25,26,40,41]. Among patients with lymphoma, resolution of chylothorax with drainage, diet, and chemotherapy or radiation ranges from 25 to 70 percent, depending on the series. A retrospective case control study of 10 patients with malignant chylothorax found a favorable response to outpatient use of an indwelling pleural catheter, compared with repeated thoracenteses, a pleuroperitoneal shunt, or talc pleurodesis [42]. A single case study reported that chylothorax due to chronic lymphocytic leukemia responded to ibrutinib [43].

PATIENTS WHO FAIL MEDICAL THERAPY — For patients not responding to conservative therapy, definitive intervention is warranted [40]. Options include pleurodesis, percutaneous thoracic duct embolization or disruption (TDE/TDD), lymphangiography with highly viscous iodinated poppy-seed oil (Lipiodol, ethiodized oil), surgical thoracic duct ligation (TDL) caudal to a leak, thoracic duct reconstruction, combinations of TDL/glue closure, or TDE/TDD with chemical pleurodesis.

Selecting an intervention — Selection of an interventional modality is individualized and depends upon multiple factors including the etiology of chylothorax (table 1) as well as local surgical and interventional radiologic expertise and preference, the rate of chyle loss, the likelihood of response to the chosen intervention, location of lymph leakage or thoracic duct obstruction, the risk of surgery, and patient preferences [7,12,18,44]. Advanced imaging techniques, such as contrast-enhanced dynamic magnetic resonance lymphangiography and intranodal computed tomography lymphangiography may assist selection of a therapeutic approach [45-47], although they are reserved for cases when lymphangiography is not diagnostic or cannot localize a source of a leak [46]. We typically present such patients to a multidisciplinary team of pulmonologists, thoracic surgeons, and interventional radiologists to select an appropriate intervention(s).

●For patients with high-output postoperative chyle leaks who do not respond to three to five days of conservative management, TDE/TDD or surgical interventions directed toward the thoracic duct (eg, ligation/glue closure/reconstruction) with or without pleurodesis is usually the preferred choice [8,9,12,44]. TDE/TDD is becoming preferred therapy in many institutions and is especially appropriate for patients who are poor candidates for surgical TDL [46]. (See 'Thoracic duct ligation' below and 'Percutaneous or retrograde lymphatic embolization or disruption' below and 'Pleurodesis' below.)

●For patients with a nonsurgical etiology who fail medical therapy, treatment options include chemical or surgical pleurodesis, percutaneous TDE/TDD; lymphangiography with Lipiodol; surgical thoracic duct ligation, repair, or glue closure; or combinations of these therapies (typically pleurodesis with TDL) [48,49]. As examples:

•Patients who drain lower volumes of chyle (eg, <500 mL/day) may be suitable for pleurodesis alone [18], while those who drain volumes >500 mL may be more suited for TDL, TDE/TDD, or a combination of pleurodesis and TDL. (See 'Thoracic duct ligation' below and 'Percutaneous or retrograde lymphatic embolization or disruption' below and 'Pleurodesis' below and 'Combination therapy' below.)

•Patients with chyle leak from malignancy may be treated with pleurodesis alone, since thoracic duct ligation is not generally successful in this population; reasons for this are unknown but may relate to the likelihood of being unable to repair a diseased part of the thoracic duct, anatomical variations of thoracic ducts that exist in 40 to 60 percent of patients [50], or laceration or obstruction of tributaries of the thoracic duct that are involved with malignancy. Some patients with underlying malignancies develop chylothorax from thoracic duct outlet obstruction that causes backflow of lymph into lymphatic branches that normally drain into the thoracic duct. Surgical TDL only increases the degree of thoracic duct obstruction and promotes chyle leakage from downstream tributaries. Thoracic duct repair and reconstruction may relieve or bypass the obstruction and resolve the chylothorax [44,51]. (See 'Pleurodesis' below.)

•Patients who have a patent and intact thoracic duct on lymphatic imaging and who have chylothorax from abnormal retrograde lymphatic flow or lymphatic vessel malformations that direct flow to the lungs may respond to TDE/TDD of retroperitoneal lymphatics rather than TDL. For those with lymphatic masses (which often overproduce lymph), embolization of the masses while keeping the thoracic duct patent is also appropriate. (See 'Percutaneous or retrograde lymphatic embolization or disruption' below.)

•Contrast-enhanced lymphangiography with Lipiodol may be therapeutic, perhaps due to the sclerosing effects and temporary "oily" occlusion of lymphatics by the contrast agent. Case reports and case series report a high success rate for various etiologies of chylothorax including refractory postoperative chyle leaks [46,52-55]. (See "Etiology, clinical presentation, and diagnosis of chylothorax", section on 'Lymphatic imaging in select patients'.)

Modality options

Pleurodesis — For patients who fail conservative therapies in whom early thoracic duct intervention is not indicated (eg, those with low-volume postoperative chyle leak), pleurodesis is an option. For those in whom pleurodesis is selected, options include chemical pleurodesis with talc instillation by a chest drainage catheter or other chemicals (eg, bleomycin, hypertonic glucose, or doxycycline), and surgical pleurodesis (eg, abrasion, chemical insufflation, pleurectomy) at the time of thoracoscopy or thoracotomy [8]. Choosing between medical or surgical pleurodesis is dependent upon the ability of the patient to tolerate surgery and patient preference, but in general, surgical pleurodesis is more effective than chemical pleurodesis by a chest tube in this setting. The details of pleurodesis are described separately. (See "Chemical pleurodesis for the prevention of recurrent pleural effusion".)

Because the success of pleurodesis generally depends on adequate drainage of the pleural space prior to the introduction of chemical or talc, concomitant thoracic duct intervention such as embolization or ligation is commonly performed (surgical or percutaneous) [8]. Thus, data to support the success of pleurodesis alone are limited:

●For patients with postoperative chyle leaks, success rates vary from 80 to 100 percent [12,18,56]. One series of 37 patients with chylothorax after thoracotomy reported that 80 percent of patients with persistent chylothorax after conservative measures who had a pleural fluid output of 300 to 500 mL/day responded to pleurodesis with OK-432 (a lyophilized preparation of Streptococcus pyogenes) [12]. Patients with >500 mL/day of pleural fluid output responded to surgical interventions. In the setting of high-volume postsurgical chylothorax (eg, >1 L/day), TDE or TDL are generally considered the treatment of choice, and therefore, no data are available regarding pleurodesis without TDE or TDL in this population. Another case series of 67 patients with chylothorax after lung resection demonstrated success with pleurodesis as the only intervention in all 27 patients for whom 32 pleurodeses were performed [18]. (See 'Thoracic duct ligation' below.)

●In the setting of nonsurgical chylothorax, case series of patients who underwent pleurodesis alone generally revealed a success rate between 80 and 100 percent [8,57]. For patients with a malignant chylothorax, pleurodesis (usually chemical) is favored over surgical ligation of the thoracic duct because malignant chylothorax does not usually benefit from ligation of the thoracic duct [57]. However, case series have reported mixed results with pleurodesis in patients with malignancy with some case series of patients with malignant chylothorax reporting high success rate with pleurodesis (up to 100 percent) [57,58], and others reporting failure [8,42,59].

Percutaneous or retrograde lymphatic embolization or disruption — Percutaneous catheterization and embolization (TDE) or needle disruption of the thoracic duct, cisterna chyli (figure 1 and figure 2), lymphatic masses, or prominent retroperitoneal lymphatic ducts (TDD) have been employed in patients with both traumatic and nontraumatic chylothorax [46,60-72]. TDE has the advantage of being able to identify the leak and offer a therapy in the same setting and is less invasive when compared with surgical TDL [46]. These techniques are increasingly used for management of chylothoraces as an alternative to TDL, chylothoraces that fail to respond to pleurodesis alone (eg, TDL may be difficult to perform in those who have had previous pleurodesis since accessing the thoracic duct on the pleurodesed side can be challenging), suspected intra-abdominal chyle leaks from the cisterna chyli, and chylothoraces in patients who are poor operative candidates [70,73]. However, effectiveness is dependent on local expertise, although their availability is rapidly increasing in both private and academic medical centers [74]. Among the many procedures available, TDE/TDD represent the most commonly performed.

Initial lymphangiography with ultrasound-guided intranodal lymphatic cannulation allows visualization of large retroperitoneal lymphatics, which are then most commonly accessed by transabdominal percutaneous needle cannulation [46]. Some centers access the thoracic duct in a retrograde manner via a subclavian vein approach [67,75] or by transnodal lymphangiography via groin nodes [76] when a transabdominal approach is unsuccessful or unfeasible. Other approaches have been reviewed in the literature [73] with case reports demonstrating success with percutaneous thoracic duct scleroembolization guided by computed tomographic-lymphangiography [77] and magnetic resonance imaging-lymphangiography [72]. The transpedal technique was previously the primary access point for lymphangiography, but it is becoming obsolete because of the less laborious and safer approaches now available with image guidance [10,46].

●Thoracic duct embolization (TDE) – After cannulation of the cisterna chyli, a catheter is advanced into the thoracic duct with instillation of contrast to localize the leak. The affected thoracic segment is then embolized with coils and surgical "glue" [46,60,66,67,78].

●Thoracic duct disruption (TDD) – TDD is performed for patients who have technical issues that do not allow percutaneous lymphatic access for TDE. The goal of TDD is to macerate the cisterna chyli or major lymphatic channels, thereby decreasing lymphatic flow to allow caudal lymphatic leaks to heal [46,61,79,80].

TDE has previously been technically challenging, but experience with this procedure is becoming widespread. In centers with expertise, approximately 70 to 90 percent of patients with chylothorax from a variety of etiologies experience a successful procedure on the first attempt [46,67,78].

Although clinical experience with TDE/TDD is rapidly increasing, randomized trials comparing it with TDL have not been performed. Success rates derived from case series vary. In patients with traumatic and nontraumatic chylothoraces who underwent TDE or TDD, clinical success rates were 72 percent for TDE and 55 percent for TDD with higher rates of clinical response for traumatic (62 versus 13 percent) as compared with nontraumatic (13 percent) chylothoraces [67]. Other series limited to patients with traumatic chylothoraces report a complete or partial success rate with TDE/TDD of 71 to 88 percent [46,63,66,78]. Success rates for TDE alone for patients with traumatic chylothorax have been reported as high as 90 percent [46,66,81]. For patients with nontraumatic chylothoraces, success of TDE has been reported to be highest (75 percent) when lymphatic obstruction is demonstrated by lymphangiography to be at the level of the thoracic duct [68].

Immediate postprocedure complications are usually minor (bleeding and pain at the injection site) and occur in less than 7 percent of patients [46,60,64,67,79]. Leg swelling and chronic diarrhea are the most common delayed complications each occurring in eight percent of patients. Other complications include lung parenchymal bleeding, embolization of lipiodol to the pulmonary circulation, and infection at the catheter injection site. (See "Etiology, clinical presentation, and diagnosis of chylothorax", section on 'Lymphangiography'.)

Wider experience is needed to determine other clinical factors that predict a response. As an example, patients with nontraumatic chylothorax and lymphatic masses may have patent thoracic ducts on lymphangiography and may not respond to TDE because chylothorax results from overproduction of lymph, weeping of lymph from diseased lymph nodes into the pleural space, or leakage from malformed or disrupted lymphatic channels within or near the region of the lymphatic masses. However, these patients may benefit from direct injection of the lymphatic masses during the procedure instead of embolization [82].

Thoracic duct ligation — TDL is best suited for those who have a high-volume chyle leak due to a laceration of the thoracic duct in a postoperative setting (eg, >1 L per day most commonly following esophagectomy, cervical procedures, or lung resection [7,8,25,83]) or patients with high-volume leak due to liver cirrhosis. However, TDL can also be successful in nonsurgical patients with low-volume leak who have failed conservative therapy, although outcomes are less certain.

TDL is performed via video-assisted thoracoscopy or open thoracotomy depending on local expertise and is the preferred method for visibility of the thoracic duct [9,24,84]. However, locating (and repairing) the leak during surgery may be challenging due to tissue inflammation and adhesions. Thus, localization of the leak using one of a variety of lymphangiography imaging techniques is valuable prior to proceeding. In addition, identification of the thoracic duct intraoperatively may be facilitated by preoperative (20 minutes prior to induction of anesthesia) or intraoperative administration of dairy cream or another fat load (eg, olive oil) alone or mixed with a lipophilic green dye via nasogastric or nasojejunal tube. If the anesthesiologist does not allow any oral intake before induction, patients can be served ice cream before midnight the day before surgery [3]. Some surgeons avoid routine preoperative administration of dyes because they stain the operative field, which can especially complicate thoracoscopic TDL [85]. Bilateral inguinal injection of indocyanine green with albumin, however, may assist identification the site of a leak during thoracotomy or thoracoscopy [86,87].

Access to the thoracic duct is usually ipsilateral to the chylothorax because that side is typically the location of the thoracic duct tear. In addition, accessing the ipsilateral hemithorax allows mechanical or chemical pleurodesis to be performed on that side during the operation. However, other considerations regarding the surgical approach may influence the choice of which side to enter, such as the exact course of the thoracic duct in that patient, the side of the initial surgery, or the ease or difficulty of a left-sided approach in patients who have a gastric conduit following esophagectomy.

Sutures or clips are placed on both sides of an identified tear; when the exact leakage site is unclear during surgery, the duct is usually ligated or clipped just cephalad to the aortic hiatus [9,24]. In addition, a sealant or fibrin glue is sometimes applied to the area of ligation [24,88]. Extensive dissection to identify the site of leakage is discouraged because this may create additional thoracic duct leakage sites [25]. If a leak cannot be identified, thoracoscopic mass ligation of the duct is sometimes performed above the esophageal hiatus between the aorta, vertebral bodies, and pericardium. When the chyle leak is found to be subdiaphragmatic based upon thoracoscopic examination or lymphatic imaging, a laparoscopic approach is used to ligate the cisterna chyli (figure 1) at the point of entry into the thoracic cavity [89].

TDL is an effective procedure. TDL for postoperative chylothorax is associated with a 90 percent success rate [8]. Whether it is as successful in those with nontraumatic chylothorax is unknown but in our experience, this population does not have the same degree of success with ligation as those with traumatic chyle leak.

Despite the reported success rate, TDL has a morbidity and mortality of 38 and 2 percent, respectively, when performed for postoperative chylothoraces. Lymphedema is a known complication of TDL, but usually resolves over several months as collateral lymphatic-venous communications develop [90]. In postoperative patients, untreated chylothorax has a mortality that ranges from 50 to 80 percent and ligation reduces mortality in the range of 10 to 16 percent [8,91,92].

Combination therapy — Many clinicians perform concomitant pleurodesis in patients undergoing TDL since both procedures can be performed in the same setting without significantly increasing the procedural risk. There are no absolute indications for this combination. In addition, although outcome with this combination appears to offer the most success, data are not reliable [8,9,93]. Thus, the inclusion of pleurodesis with surgical TDL is left to surgeon discretion [8,9]. Pleurodesis may also be combined with TDE/TDD but outcomes using this approach are unknown.

Less well-established options — For patients with refractory chylothorax, therapies including adjunctive medications (see 'Adjunctive therapies' above), if not already instituted, and mechanical shunts have been reported in multiple case series, but no randomized controlled trials exist to define their role. (See 'Pleuroperitoneal or pleurovenous shunt' below and 'Others' below.)

Pleuroperitoneal or pleurovenous shunt — Pleuroperitoneal or pleurovenous shunting of chylous pleural fluid is an option after failure of other types of intervention (eg, pleurodesis with or without percutaneous TDE/TDD or surgical TDL) or for those who have failed conservative management but are poor candidates for more invasive interventions [94-97].

●Pleuroperitoneal shunts – Pleuroperitoneal shunts divert chyle from the pleural space to the peritoneum; it is postulated that peritoneal chyle returns to the venous circulation via absorption through peritoneal omentum or via the lymphatic stomata on the underside of the diaphragms [98,99]. Two types of pleuroperitoneal shunts are available: an active version that requires frequent activation of a manual pump (Denver pleuroperitoneal shunt) and a passive version (LeVeen pleuroperitoneal shunt) [96]. Pleuroperitoneal shunting was successful in a patient with a refractory high-volume chylothorax that developed after transhiatal esophagectomy [96]. On the other hand, it was unsuccessful in a patient with yellow nail syndrome who developed worsening abdominal distension and lower extremity edema; however, pleurovenous shunting was successful in that patient [95]. Pleuroperitoneal shunting is contraindicated in patients with chylothorax due to chylous ascites.

●Pleurovenous shunting – Pleurovenous shunting of chylous fluid from the pleural space to the subclavian or jugular vein has been successful in isolated patients with lymphangioleiomyomatosis, yellow nail syndrome, and postsurgical or post lung transplant chylothorax [95,97,100].

The advantage of shunts is that they are less invasive than TDL and when compared with continued drainage they prevent the loss of nutrients. However, complications include shunt occlusion, infection, skin erosions, pneumoperitoneum, and shunt migration [96,97].

The advent of TDE has supplanted the need for most of these less well-established options.

The role of transjugular intrahepatic portosystemic shunt (TIPS) in patients with chylothorax and cirrhosis is discussed below. (See 'Chylous ascites' below.)

Others — Other isolated or anecdotal cases have reported success with the following:

●Omental flap – One case report described the treatment of a chylous effusion with a pleuroperitoneal window and omental flap [101]. This procedure promotes chyle resorption by juxtaposing abdominal omentum between the pleural space and the peritoneum. It may also prevent chyle from moving in to the pleural space.

●Decortication – Decortication is a surgical approach to producing symphysis of the lung to the chest wall to obliterate the pleural space and prevent reaccumulation of a chylothorax [102]. We reserve decortication for patients who have failed prior thoracic duct ligation and pleurodesis.

●Radiation – Radiation for postoperative chylothorax has been proposed based upon the success in the management of malignant chylothorax and inguinal lymphatic fistulas [103,104].

SPECIAL POPULATIONS

Lymphangioleiomyomatosis — Lymphangioleiomyomatosis (LAM) is complicated by chylous effusions in about 10 to 20 percent of patients. In conjunction with first line therapies, sirolimus (also known as rapamycin) can decrease the size of or entirely resolve chylothoraces in this population, the details of which are discussed separately. (See "Sporadic lymphangioleiomyomatosis: Treatment and prognosis", section on 'Chylothorax and chylous ascites'.)

Chylous ascites — Patients with chylothorax due to chylous ascites do not respond to pleural drainage or second line therapies, although drainage is rarely indicated should patients become severely symptomatic or hypoxemic due to the effusion. Importantly, embolization, disruption, or ligation of the thoracic duct almost invariably worsens chylous ascites. However, the underlying cause should be treated, and dietary measures instituted. (See 'Dietary modification' above and 'Treatment of the underlying condition' above.)

In some cases, when the cause is unknown, a lymphatic interventional expert should be consulted since some patients may respond to local interventional therapy.

One case report in a patient with chylous ascites and cirrhosis reported successful treatment of chylothorax with a transjugular intrahepatic portosystemic shunt (TIPS) [105].

Lung transplantation — When chylothorax presents after lung transplantation, it is often associated with LAM. Chylothorax following lung transplant is classically refractory to conservative therapy but may respond to rapamycin in those with LAM. A spectrum of therapies has been tried, including thoracic duct ligation, octreotide, and pleurovenous shunting. (See 'Somatostatin and octreotide' above and 'Pleuroperitoneal or pleurovenous shunt' above and "Pleural complications in lung transplantation", section on 'Chylothorax' and "Sporadic lymphangioleiomyomatosis: Treatment and prognosis", section on 'Lung transplantation'.)

Central vein thrombosis — Central venous obstruction represents a rare cause of chylothorax. Patients with chylothorax of unclear etiology should be evaluated for central venous obstruction and considered for vascular recanalization and/or stenting, which has been reported to resolve chylothorax in this setting [106].

SUMMARY AND RECOMMENDATIONS

●Introduction and general principles – Chylothorax is the accumulation of chyle in the pleural space. Chylothorax can be due to multiple etiologies, among which malignancy and surgical trauma are the commonest (table 1). No algorithm has been universally adopted for the management of patients with chylothorax, since multiple clinical factors unique to each patient impact therapy including etiology (table 1), symptoms, local expertise, and rate of chyle accumulation. (See 'General principles' above and "Etiology, clinical presentation, and diagnosis of chylothorax", section on 'Pathogenesis and etiology'.)

●Postoperative chyle leaks – Management varies depending on whether the leak has a high or low output.

•High output – For most patients with high-output (ie, >1 L per day) postoperative chyle leaks, our approach is the following (see 'Management of postoperative chyle leaks' above):

-We suggest early intervention rather than prolonged conservative therapy with chest tube drainage and dietary modification (Grade 2C). The rationale for this approach is that these patients are likely to have major thoracic duct injury which is unlikely to close spontaneously, rather than leaks that originate from smaller thoracic duct tributaries which are more likely to undergo spontaneous closure. A special consideration is the postpneumonectomy patient who should not undergo pleural drainage (unless mediastinal shift to the contralateral side is present) and who should proceed directly to a therapeutic intervention such as surgical ligation of the thoracic duct or percutaneous thoracic duct embolization (TDE). (See 'Evaluation for early intervention (high output)' above.)

-While awaiting surgery (typically within the first one to five days), patients are treated with continued drainage via chest tube thoracostomy and complete bowel rest by the administration of parenteral nutrition. In addition, we suggest somatostatin/octreotide to reduce the flow of chyle through the leak, although these drugs usually do not resolve high-output chyle leaks (Grade 2C).

•Low output – For most patients with low-volume (ie, <1 L per day) postoperative chyle leaks or with chylothorax for nonsurgical reasons (eg, malignancy), we suggest conservative therapy while the underlying disorder is being addressed rather than more invasive options (eg, pleurodesis with or without percutaneous TDE, or surgical inventions) (Grade 2C). Conservative therapies involve pleural drainage for symptom control (eg, thoracentesis, tube thoracostomy, indwelling catheter), administration of octreotide, and dietary modification (low-fat diet or total parenteral nutrition). (See 'Patients not in need of early intervention (low output)' above.)

●Medical therapy – For patients receiving conservative therapy, symptoms, chyle output (or rate of reaccumulation) and chest radiograph and/or computed tomography should be obtained within a few days of initiating this strategy to assess the response.

•In the postoperative setting, more aggressive therapy is typically warranted if a chylothorax persists for more than two weeks despite these measures, or sooner if the fluid output exceeds 1 L/day for, at most, five consecutive days, or when severe metabolic or nutrition derangements appear likely to occur.

•In the nonsurgical setting or in those with slow accumulation of chyle, waiting for longer periods to note a response may be more appropriate. Success rates with conservative therapy are variable ranging from 25 to 80 percent with patients who have low-output leaks more likely to respond than those with high-output leaks. (See 'Monitoring the response' above and 'Efficacy' above.)

●Failed medical therapy – For patients with chylothorax who do not respond to or only partially respond to conservative measures, options include surgical or medical pleurodesis, percutaneous TDE/thoracic duct disruption (TDD), reconstruction of an obstructed thoracic duct, lymphangiography with highly viscous contrast (Lipiodol), or thoracic duct ligation (TDL). Selection of an interventional modality should be individualized and depends upon the underlying etiology (table 1), available expertise, rate of chyle loss, likelihood of response to the chosen intervention, interventional risk, and patient preferences. A multidisciplinary team should facilitate decision making. In general, the following principles of management are reasonable (see 'Patients who fail medical therapy' above):

•Postoperative patients who fail medical therapy – For patients with postoperative chyle leaks who fail medical therapy, percutaneous TDE/TDD or surgical (thoracotomy or thoracoscopy) TDL is indicated if the leak is shown by imaging studies to arise from a laceration of the thoracic duct. Thoracic duct reconstruction may be considered for an obstructed thoracic duct. For those who undergo TDL, pleurodesis may be simultaneously performed since this combined approach may offer the best success. (See 'Selecting an intervention' above.)

•Nonsurgical patients who fail medical therapy – For nonsurgical patients who fail medical therapy, invasive therapy should be individualized. (See 'Modality options' above.)

As examples:

-Patients who drain <500 mL/day may be suitable for pleurodesis alone, while those who drain >500 mL may be more suited for TDE/TDD or TDL with or without pleurodesis.

-Patients with chyle leak from malignancy are often treated with pleurodesis alone, since TDL is not generally successful in this population.

-Patients who have a patent and intact thoracic duct on lymphatic imaging and have chylothorax from abnormal retrograde lymphatic flow or lymphatic vessel malformations that direct flow to the lungs may be suited to embolization of retroperitoneal lymphatics rather than TDL.

-For those with lymphatic masses (which often overproduce lymph), embolization of the masses is also appropriate. Therapeutic lymphangiography with Lipiodol may benefit select patients.

•Other options – Less well-established options, including pleurovenous and pleuroperitoneal shunting, may be of value in those who are poor candidates for TDL or TDE/TDD or in those who have chylothorax refractory to invasive therapies. (See 'Less well-established options' above.)

●Special populations – Populations that require special consideration include patients with lymphangioleiomyomatosis, who should be treated with sirolimus; patients with chylous ascites, who should avoid chest tube drainage or invasive therapies such as pleurodesis, TDL, or TDE/TDD which can worsen chylothorax; and lung transplant patients who need individualized attention. (See 'Special populations' above.)