Lymphatic Leakage Treatment & Management
- Author: Michael Omidi, MD, FACS; Chief Editor: John Geibel, MD, DSc, MSc, MA more...
Medical therapy is indicated for low-volume lymphatic leakage. High-output lymphatic leakage is associated with 50% mortality when intervention is not initiated in a timely fashion and medical therapy is improperly prolonged because of nutritional, immunologic, or metabolic deterioration.[8, 12, 20, 25, 11, 29, 30, 31, 32, 33]
For this reason, we discourage the use of the term conservative management to describe medical treatment of chylous leakage. Prolongation of medical treatment and delay of interventional or surgical therapy in a patient with high-output failure can be lethal, and by no means should this be described as a conservative approach.
Patients with lymphatic fistulas should be treated individually on the basis of the amount of leakage and the type of fistula. Nutritional status should be evaluated and supported as needed; a depleted nutritional state can increase the risk of opportunistic infections. Routine antibiotic therapy is not indicated; however, a low decision threshold should be maintained for working up and aggressively treating any infections that may arise. If the leak is in close proximity to a foreign object or implant, then antibiotics may be considered.
Nutritional status can be optimized with the administration of a low-fat, high-protein, medium-chain triglyceride diet. In severe cases, complete bowel rest and TPN may be required.
Drainage of the fluid should be ensued immediately by paracentesis, thoracocentesis, or chest tube thoracostomy. The loss of fluid and fats must be calculated and replenished.
Pharmacologic agents (eg, somatostatin) have also been used successfully in the treatment of chylous ascites.[34, 35] In addition, octreotide, a synthetic polypeptide analogue of somatostatin that inhibits the secretory action of lymph fluid secretion, has been shown to be a beneficial adjunct.[36, 37]
Midodrine is a oral selective alpha-adrenergic drug that may have effects on the contraction of smooth muscles, leading to decreased chyle flow.[38, 39] Other medications (eg, orlistat and etilefrine) have also been evaluated and may be of additional benefit in conjunction with bowel rest, TPN, and drainage.
Pleurodesis with minocycline has also been described as a technique for refractory chylothorax.
Diagnostic and therapeutic lymphangiography
Lymphangiography is a diagnostic tool used to identify chylous leakage; in addition, it has therapeutic properties in stopping lymphatic leakage. The following two techniques have been described:
Bipedal cutdown (the traditional approach)
Bipedal cutdown involves injecting 1% isosulfan blue intradermally between the first and second web spaces in both feet. After 30 minutes, the lymphatic channels are identified, cut down with superficial dissection, and cannulated with a 30-gauge catheter. Ethiodized oil is infused into the catheter at a rate of 0.5 mL/min (total, 12 mL). Spot fluoroscopy is obtained to confirm adequate anterograde flow. Once this infusion is complete, normal saline is infused at the same rate. Radiographic visualization of contrast leak is followed by computed tomography (CT).
Intranodal injection obviates the necessity for cutdown and cannulation of the lymphatic channels. It has proved particularly useful in the pediatric population; cannulation of the lymphatics, which is technically challenging to begin with, is especially so in infants and children.
This procedure involves inserting a needle in the central portion of a lymph node, in the transitional zone between the cortex and the hilum of the lymph node. Contrast material is injected in small amounts and visualized under ultrasonography. Swelling of the node, lack of perinodal leak, and visualization of microbubbles indicate that the lymph node is successfully cannulated and contrast is flowing through the efferent portion of the lymphatics. Ethiodized oil contrast is then injected in small amounts (1-3 mL).
Lymphangiography is a therapeutic option for patients with lymphatic fistula, chylothorax, or chylous ascites in whom medical therapy and drainage have failed.[12, 13, 41, 1, 2, 24, 25] Reported success rates are in the range of 51-64%.[12, 13, 1] The therapeutic properties of ethiodized oil contrast have been ascribed to its granulomatous and inflammatory properties upon extravasation from lymphatic vessels.[2, 10]
In a retrospective study, eight patients with groin lymphatic leakage, chylothorax, and chylous ascites were evaluated. All of them had failed therapy with diet modification, parenteral nutrition, and drainage. Overall success and drain removal were noted in six of the eight patients (75%) with therapeutic lymphangiography.
In another study, seven of 22 patients presented with chylothorax, eight with lymphatic fistula, three with lymphocele, and one with chyloperitoneum. Of the 20 patients treated, 11 (55%) needed no further surgical intervention and were successfully treated with ongoing drainage and TPN. Patients with lymphatic fistulas had the highest success rate (75%), followed by those with chylothorax (57%) and those with lymphocele (0%). Treatment failed in two of the 22 patients (9.1%) because of inability to cannulate lymphatic vessels.
A study of 14 patients with chylotorax and chylous ascites who had failed medical therapy for at least 1 week and whose output exceeded 200 mL/day reported success in nine cases (64%). In seven patients whose daily output decreased by more than 50% after medical therapy and drainage. complete resolution was achieved with the addition of lymphangiography (85.7%).
Sclerotherapy is a technique used to treat refractory lymphatic leakage. Doxycline, ethanol,[12, 43, 44] and minocycline have all been successfully used to treat lymphatic leakage. The procedure involves performing lymphangiography with ethiodized oil contrast to identify the location of the fistula, chylothorax, or chyloperitoneum. CT is performed 4-5 hours after injection of ethiodized oil. Patients with leaks around blood vessels or nerves are not treated with sclerotherapy.
A review of 18 patients with persistent lymphatic leakage who were treated with lymphangiography and sclerotherapy found that treatment was successful in 13. Some of the success could be attributed to the therapeutic lymphangiography. Five patients underwent delayed sclerotherapy, which was successful in three (60%). Notably, two of the three patients in whom sclerotherapy was successful had high-output leakage (>1000 mL/day).
In general, therapeutic lymphangiography is not effective in patients who have high-output lymphatic leakage; however, sclerotherapy can be an effective initial therapy in this category of patients.
Thoracic duct embolization
Thoracic duct embolization is a procedure developed as a minimally invasive alternative to thoracic duct ligation.[18, 17, 45] The technique involves pedal or intranodal lymphangiography followed by cannulization of the cisterna chyli/thoracic duct and embolization with coils or the use of N-butyl cyanoacrylate glue.
In a series of 109 patients, Itkin et al reported success rates of 73.8% for traumatic and surgical lymphatic leaks and 70.6% for nontraumatic causes (overall success rate, 71%). The investigators noted a 16% failure rate with just embolization and a 9% failure rate with embolization and the use of N-butyl cyanoacrylate glue. Catheterization was successful in 73 patients (67%). The complication rate was 3%.
Cope and Kaiser reported a 73.8% success rate of lymphatic leakage with thoracic duct embolization in their series of 42 patients.
To perform thoracic duct embolization, moderate anesthesia is used. Prophylactic antibiotics are administered. Next, 1% isosulfan blue with 1% lidocaine is injected into the soft tissues of the dorsum of the foot to identify lymphatic channels. These channels are dissected via horizontal incisions and cannulated with a 30-gauge needle.
Diagnostic pedal lymphangiography using ethidiozed oil is performed with a lymphangiogram pump. Approximately 15 mL of contrast is injected, followed by 20 mL of normal saline. The target vessel is identified, which is the thoracic duct, the cisterna chyli, or one of the tributaries.
A 21- or 22-gauge 15- to 20-cm Chiba needle is introduced via a transabdominal approach to access the vessel. Care is taken to avoid the aorta or large intestines. A 0.018-in. guide wire is advanced through the needle into the cisterna chyli and further into the thoracic duct. A 65-cm microcatheter is introduced over the guide wire while water-soluble contrast is injected to identify the leak. The catheter is replaced with embolization coils and later with glue mixed with ethiodized oil in a 1:2.5 ratio.
Thoracic duct disruption
If extravasation of lymph is demonstrated without a definite cisterna chyli, needle laceration of the ducts is performed at the junction of the thoracic duct to the cisterna chyli. This is thought to create a controlled fistula to the retroperitoneum instead of the thoracic area, which eventually stops.
Thoracic duct disruption has been used for patients when embolization was impossible as a result of difficulty in cannulation or visualization of the thoracic duct or cisterna chyli. In a study of nine disruptions, the procedure successfully stopped lymphatic leakage in four patients.
The reported incidence of chylous leakage after esophagectomy is approximately 10%. The reported incidence after abdominal aortic surgery is 1%, and that for all general thoracic procedures is 0.42%.[16, 17] Early intervention is recommended, in that these leaks rarely heal with medical therapy, TPN, and drainage.
If chylous leakage is detected during the procedure, it should be addressed during the procedure. Prophylactic ligation during the procedure has been described as an effective means of preventing postoperative chylous leak. In a review of 323 patients with prophylactic ligation of the thoracic duct during esophagectomy, the authors reported no postoperative chylothorax and no postoperative complications related to the procedure.
Surgical therapy is indicated for any chyle leak greater than 1000 mL/day that is not responsive to TPN, drainage, and medical therapy.
Standard preoperative care should be implemented for the surgical treatment of lymphatic fistulas, chylous ascites, and chylothorax. Careful attention to the nutritional and metabolic status of the patient is important before operative intervention. Standard blood work, electrocardiography (ECG), chest radiography, and risk stratification for cardiopulmonary status should be performed.
A surgical and interventional radiology team in a tertiary level facility is optimal. Physicians experienced in intensive care should also be available. Appropriate informed consent must be taken addressing risks, indications and alternatives of the procedure. Concerns and fears of both the patient and the family should be addressed.
Preoperatively, a lymphangiography is performed (see above). Patients should be given nothing orally (NPO [nil per os]) for 6-8 hours before surgery; 50 mL of cream or high-fat milk is given through the nasogastric (NG) tube or ingested 4-5 hours before the procedure. Preoperative antibiotics and appropriate prophylaxis for deep vein thrombosis (DVT) should be considered.
Meticulous sterile technique must be employed. If the patient is undergoing an interventional radiology procedure, a surgical team should be available for backup. The patient should be prepared and draped so as to afford access to necessary structures in case of any emergencies.
Infrainguinal, intra-abdominal, and intrathoracic lymphatic injury may be better defined with the interdigital injection of 5 mL of isosulfan blue into the first and second web spaces of the foot. Upon infrainguinal reexploration, blue fluid droplets are emitted from the site of lymphatic injury. Infrainguinal sites of lymphatic injury should then be suture-ligated if clearly visualized (or glued with fibrin if not clearly visualized), then closed meticulously in multiple layers. Clips, sutures, or glue may be used to seal lymphatics.
A Jackson-Pratt drain may be left near the site of lymphatic injury. It should remain inside until drainage has slowed. If possible, care should be taken not to place drains close to vessels, nerves, or prostheses.
Suture ligation of the injured lymphatic (infrainguinal, lumbar, mesenteric, or para-aortic) is the treatment of choice injuries when medical and interventional therapies fail. For injured infrainguinal lymphatic vessels that are not visualized, fibrin gluing may be substituted for suture ligation. Injuries to the cisterna chyli or thoracic duct should be repaired by means of lateral closure with a 6-0 to 8-0 polypropylene suture. If this is unsuccessful, proximal suture ligation of the cisterna chyli and thoracic duct may be implemented.
Depending on the site of the lymphatic leakage, a celiotomy or a retroperitoneal approach can be taken. Lumbar, mesenteric, and para-aortic lymphatic vessels may also be suture-ligated or oversewn after identification with the isosulfan blue technique. However, injuries involving the cisterna chyli should undergo lateral closure with a 6-0 to 8-0 polypropylene suture. A Jackson-Pratt drain may be left intra-abdominally near the site of injury.
Thoracic duct injuries may be repaired primarily by means of lateral closure with 6-0 to 8-0 polypropylene. If this is unsuccessful, complete ligation of the thoracic duct may be performed. A chest tube should be left in place for any further drainage.
General anesthesia is induced, and the right lung is selectively intubated and ventilated. The patient is placed in the right lateral decubitus position. A left posterolateral thoracotomy is performed at the sixth or seventh intercostal space (ICS). Parietal pleurectomy can be a means of promoting symphysis and helping to stop the leak. Ingestion of 40-50 mL of cream or milk facilitates identification of the leak. If the leak is not readily identified, extensive dissection is discouraged; such dissection can result in additional injury to vital structures.
Mass ligation of tissues between the aorta, spine, esophagus, and pericardium can be performed starting at the level of the diaphragmatic hiatus. Optimally, the thoracic duct should be divided and ligated just above the diaphragmatic level; this stops flow from accessory ducts that may not have been recognized. Once the thoracic duct is identified, it should be dissected and double-ligated with a nonabsorbable monofilament suture.
Thoracoscopic ligation of the thoracic duct involves the placement of three ports. One port is placed for the 30 º camera in the sixth or seventh right ICS at the midaxillary line; one is placed for dissection and division of the inferior pulmonary ligament in the eighth ICS posteriorly; and one is placed for retraction of the lung in the fourth or fifth ICS at the anterior axillary line. The thoracic duct is visible after incision of the pleural reflection above the diaphragm. Ligation can be performed with monofilament nonabsorbable suture.
Postoperatively, close surveillance must be initiated, preferably in an intensive care unit, to optimize patient outcome after reoperative surgery. Qualified staff members who are familiar with reoperative infrainguinal, abdominal, and thoracoabdominal aortic surgery must be available. Special attention to drain output, chest tube output, and wound care is essential. The presence of attentive personnel to allay patient and family concerns is also helpful.
Aggressive pain control should be initiated immediately. Prophylactic antibiotics generally need not be continued for longer than 24 hours. DVT prophylaxis, consisting of systemic compression devices and low-molecular-weight heparin, should be continued as warranted by the patient's risk status. To minimize the risk of DVT, ambulation and rehabilitation should be initiated early, generally within 24 hours after the procedure. Incentive spirometry, deep breathing, and pulmonary hygiene should be initiated immediately after surgery.
The Jackson-Pratt drain should stay in place until lymphatic drainage has stopped. A chest tube may be removed once drainage diminishes to 75 mL/day and no further evidence of lymphatic injury exists.
A regular diet may be resumed once bowel function returns to normal.
Implement standard surgical follow-up care after repair of lymphatic fistulas and lymphatic injuries that result in chylous ascites and chylothorax. Lymphangiography may be performed before discharge to confirm successful operative closure of these lymphatic injuries.
After discharge from the hospital, follow patients biweekly for the first 1-2 months, then monthly for the following 6 months. Once both the surgeon and the patient are satisfied with the outcome, the surveillance interval may be extended to 3 months.
Lymphatic fistulae and lymphatic injuries resulting in chylous ascites and chylothorax are complications of infrainguinal, abdominal, and thoracoabdominal aortic reconstruction. Nonoperative or conservative management of these complications reduces morbidity and mortality.
Lymphangiography has an overall complication rate of 5.9% (pulmonary artery embolization and infection of pedal lymphangiography incision).
A survey of 106 patients who underwent thoracic duct embolization documented an overall long-term complication rate of 14.3%, including lower-extremity swelling (8%), abdominal swelling without evidence of anasarca or ascites (6%), and chronic diarrhea (12%). Patients reported the complications to be mild and not disabling.
The rate of complications specific to thoracic duct embolization (bile leak from liver secondary to Chiba needle insertion into the thoracic duct) has been 0.3%, with no mortality. Pulmonary embolism of glue has been reported, with no sequelae.
Outcome and Prognosis
In general, chylous ascites and chylothorax secondary to traumatic injury during vascular reconstruction carry a better prognosis than the same conditions occurring secondary to underlying neoplasia. A mortality of approximately 18% has been reported for chylous ascites developing after aortic surgery. Mortality figures in the range of 44-83% have been reported for chylous ascites developing secondary to an underlying neoplasm.
High-output chylous leakage is associated with a 50% mortality when surgical intervention is not promptly initiated. This high mortality is associated with nutritional, immunologic or metabolic deterioration from large-volume lymph loss; it is reduced to 10% when surgical therapy is initiated in these patients.[13, 9, 19, 20, 21, 7]
Future and Controversies
Optimal therapy for postoperative chylothorax remains controversial. In general, a low-fat diet or bowel rest, medical therapy, TPN, and drainage are warranted. High-output drainage is addressed early with interventional radiology techniques. Surgery is reserved for persistent drainage that is not responsive to lymphangiography or thoracic duct embolization. Alternative therapies have been described, such as sclerotherapy, gluing, and thoracic duct disruption.
Efforts have also been focused on ways of minimizing or preventing lymphatic leakage — for instance, prophylactic ligation of the thoracic duct during esophagectomies and endoscopic vascular reconstruction (if technically feasible).
The advent of endovascular reconstruction has limited tissue handling and dissection and has reduced the incidence of lymphatic complications. Further advancements in endovascular techniques will enable more complex procedures to be performed, with consequent reductions in operative morbidity and mortality.
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