Abstract

Background: This study aims to evaluate the incidence, treatment protocols, and impact of chylothorax on early outcomes after pediatric cardiovascular surgery.

Methods: Records of 1,123 pediatric patients who underwent heart operation at our clinic between June 2011 and June 2014 were reviewed retrospectively. Thirty-five patients (19 males, 16 females; median age 240 days; range 5 days to 15 years) who developed postoperative chylothorax were included in the study.

Results: Development of chylothorax was detected most frequently in single ventricle repairs (n=11, 31%). It was followed by aortic arch repairs (n=9, 25%), tetralogy of Fallot (n=4, 1%), atrioventricular septal defect repairs (n=4, 11%), arterial switch operations (n=3, 8%), ventricular septal defect repairs (n=2, 6%), and other operations (n=2, 6%). Median duration of drainage of chylothorax was nine days (range, 2 to 44 days). Nutritional management included low lipid diet, enteral feedings enriched with mediumchain triglycerides, and total parenteral nutrition. Fourteen patients were administered octreotide, four patients were administered thoracic duct ligation, and four patients were administered pleurodesis. Sepsis was observed in nine patients and three patients died.

Conclusion: Chylothorax developing after pediatric cardiac surgery is not a rare complication. It occurs most frequently after single ventricle repair and has a significant impact on postoperative clinical course and morbidity.

Chylothorax, which develops as a result of the deposition of fatty acids along with lymphatic fluid into the pleural cavity, is one of the reasons for postoperative morbidity.[1,2] The primary mechanisms that lead to postoperative chylothorax are direct trauma to the lymphatic vessels or the thoracic duct and secondary to central venous hypertension (HT) after a cavopulmonary connection (Glenn or Fontan). Venous thrombosis has also been reported but is less common. Prolonged chylothorax places patients at risk for malnutrition, poor wound healing, infections, fluid imbalance, electrolyte abnormalities, prolonged mechanical ventilation and device utilization, and longer stays in the hospital and intensive care unit (ICU).[3,4]

The first step in chylothorax treatment is the drainage of the pleural fluid to decrease the flow of the lymphatic fluid from the ductus thoracicus. This is followed by a low-fat or fat-free diet or the replacement of enteral food with liquid intake [nil per os (NPO)] or the use of total parenteral nutrition (TPN) including intravenous lipids.[1-3] Pharmacotherapy with the somatostatin analogue octreotide has also been proposed to decrease the blood flow to the hepatic, portal, and splanchnic circulations, resulting in a decrease in the lymphatic flow through the ductus thoracicus.[5] If medical therapy fails, surgical intervention should be considered, with thoracic duct ligation, pleurodesis, and pleural peritoneal shunting being appropriate options for persistent chylothorax.[6]

The aim of this study was to evaluate the demographics, diagnoses, primary cardiac surgical procedures, and treatment protocols of patients with postoperative chylothorax and assess their effects.

Methods

A total of 1,123 patients underwent cardiac surgery during the study period, and 35 (3.1%) of these had chylothorax in the postoperative period [19 males, 16 females; median weight 8 kgs (range 2-45 kgs); median age 8 months (range 5 days-15 years)] and were included in the study, which took place at our facility over a three-year period beginning in June of 2011. These patients were identified using the hospital medical records database.

After a retrospective review of these records, the demographic data related to age, weight, time of diagnosis, cardiac diagnosis, and primary cardiac surgical procedure as well as the data associated with chest tube output, fluid intake and output, dietary intake, medical and surgical treatments for chylothorax, hospital mortality, length of stay in the ICU and hospital, mechanical ventilation duration, number and duration of chest tube placements, duration of NPO and TPN diets, and bloodstream infections were recorded. In addition, we also noted the Risk Adjustment for Congenital Heart Surgery (RACHS-1) category scores.[7] The diagnosis o f p ostoperative c hylothorax was carried out by investigating the characteristics of the pleural fluid, and a triglyceride level of >110 mg/dL or a white cell count (WCC) of >1,000 cell/μL with a significant lymphocyte fraction (80%) confirmed its presence.[4,8] The onset of chylothorax was considered to be the point at which diagnostic fluid was first recovered.

The instutional protocol for the management of postoperative chylothorax was followed during the study period. Chest tube drainage of ≤5 mL/kg/day was classified as low volume while >5 mL/kg/day was considered to be high volume. All of the patients diagnosed with chylothorax were fed with only medium chain triglyceride (MCT) oil-based formulas, and the same food was provided to those who showed persistent low volume drainage. Octreotide treatment was started when the drainage did not diminish to a volume of <2 mL/kg/day after three to five days of NPO followed by TPN administration. For the patients with high volume drainage, oral feeding was stopped, and TPN was given directly. In addition, intravenous octreotide infusion was added to the treatment in cases that were unresponsive to TPN alone. When the drainage decreased to <2 mL/kg/day, the MCT oil-based formulas were added to the diet without the octreotide infusion for another one or two weeks until the chylothorax ceased, and then the chest tubes were removed. Pleurodesis was applied to some of the patients when the amount of drainage was >10 mL/kg/day at the end of 10 days of treatment via 500 mg vancomycin in a 50 mL saline solution. This was given through the chest catheter or tube with the patient positioned toward the left or right lateral decubitus in both the face down and supine positions for 10 minutes each. The chest catheter was kept closed for 24 hours. The patients who did not respond to conservative management after two to three weeks were evaluated for thoracic duct ligation, which was then applied directly to some patients without pleurodesis. Additional recommendations included an echocardiogram to determine whether correctable abnormalities were present, the monitorization of serum albumin and C-reactive protein (CRP) levels, hemocoagulation, a hemogram, a biochemical analysis, and daily chest X-rays. Additionally, 14 or 16 G single-lumen venous catheters were chosen for delayed chylothorax drainage instead of regular chest tubes.

Statistical analyses
The statistical evaluation of the data was performed by using the SPSS for Windows version 15.0 software program (SPSS Inc., Chicago, IL, USA). Categorical variables were presented as absolute and percent frequencies, whereas quantitative variables were given as medians and ranges. The Mann-Whitney U test was used to compare the mean values between the groups while chi-square and Fisher’s exact tests were performed to compare the rates between the groups. Statistical significance was set at p<0.05.

Results

The primary diagnoses of the the 35 patients with chylothorax included 11 patients with complex lesions (treated with cavapulmonary connection), five with hypoplastic left heart syndrome (HLHS), four with atrioventricular septal defect (ASD), four with tetralogy of Fallot, three with transposition of the great arteries, two with ventricular septal defect (VSD) and six with other simple lesions. The patient characteristics and procedures are listed in Table 1.

Table 1: Demographic and clinical characteristics of the patients diagnosed and treated for chylothorax

Surgery was performed via a median sternotomy in 28 patients and a thoracotomy in the other seven. The median duration of the initial mechanical ventilation was two days and ranged from less than 1 day to 18 days. Six patients required re-intubation, and two died before ever being extubated. Excluding the three patients who died, the median initial ICU length of stay was seven days (range 1-30 days), but four patients required readmission to the ICU. Furthermore, the median total postoperative length of hospital stay for the 32 survivors was 25 days (range 7-64 days), including the subsequent readmission of the four patients for persistent or recurrent chylothorax.

The chylous pleural effusion was in the right chest in 18 patients (51%), the left chest in 17 others (49%), and on both sides in six more (17%). Four patients (11%) also had additional pericardial effusion.

The median time for diagnosing the chylothorax was six days (range 1-28 days) after the surgery, with 20 patients being diagnosed within seven days after the operation and 15 after the postoperative seventh day. Among those with an early diagnosis, five did not have chest tubes at the time of their diagnosis, whereas 15 did. None of the patients who were diagnosed later had chest tubes, and for them, the chylothorax was diagnosed by a clinical examination, a chest X-ray, and the testing of fluid samples by pleurocentesis. The median drainage on the day of diagnosis was 10 mL/kg (range 4-36 mL/kg), and the median drainage time of the chylothorax was nine days (range 2-44 days).

The chylothorax was evident from the laboratory testing of the fluid in 21 patients (60%) because of the presence of a triglyceride concentration of >110 mg/dL. Moreover, 18 patients underwent additional testing of the fluid cell counts, and this showed that nine (50%) had a total white blood cell (WBC) count of over 1,000 cells/mm3. In addition, the percentage of lymphocytes was more than 80% in 13 of the patients (72%), and two had at least one of the three fluid abnormalities. However, we found no significant differences between the characteristics of chylous drainage after the cavapulmonary connection procedures and those that developed after other surgeries (Table 2).

Table 2: Characteristics of the clinical course of the patients who underwent cavopulmonary connections versus all other patients

Nutritional management included the use of MCTs for all 35 patients. Total parenteral nutrition was used for 23 patients, and octreotides were used in 14. In four patients who did not respond to these therapies, pleurodesis was performed, and one of these was also treated with thoracic duct ligation. The medical and surgical treatments for the chylothorax are listed in Figure 1.

Figure 1: Flowchart showing the management strategies and outcomes for the patients diagnosed with postoperative chylothorax. MCT: medium chain triglyceride; TPN: Total parenteral nutrition.

In addition, nine patients had sepsis, and five had arrhythmias and a pneumothorax. All of the complications are summarized in Table 3. Three patients died during their initial hospital stay at the postoperative 10th, 30th, and 42nd days because of chronic lung disease and sepsis, without any resolution of their chylothorax. Furthermore, two of the patients who did not survive underwent a Norwood stage 1 operation, and one underwent an arterial switch operation. No surgical intervention was performed for the chylothorax in these patients.

Table 3: Comparison of early postoperative complications

In four patients, chylothorax developed after they were discharged, and it was determined that all of these had a single-ventricle pathology. One of them was treated with ductal ligation, and two received pleurodesis, with both showing improvement with the use of octreotides and TPN. One patient treated with medical therapy.

Discussion

The incidence of chylothorax from various centers in different years has varied. Allen et al.[9] reported an incidence rate of 1% in their study in 1979 and 1987 while the latest reported incidence rates were 3.5% by Chan et al.[3] and 5% by Ismail et al.[10] The higher rates were likely due to the increased complexity of the patients along with the number of singleventricle repairs and redo surgeries.[3] The incidence of chylothorax in our study population was 3.1%, which was in line with the more recent studies. Furthermore, 45% of our cases involved single-ventricle repairs. Five of these patients had HLHS, and four underwent redo surgeries. Chan et al.[3] reported that chylothorax is mostly seen in heart transplantation operations and patients with Fontan circulation. In our study, the single-ventricle surgeries were most frequently complicated by chylothorax (n=11, 31%) followed by arch repairs (n=9, 25%); VSD repairs (n=2, 6%), ASD repairs (n=4, 11%), arterial switch repairs (n=3, 8%), and other types of repair (n=2, 6%). However, heart transplantations are not performed at our center.

The limited number of patients studied in each series precludes having a consensus regarding which protocol is the most effective, and there is limited data related to the treatment of postoperative chylothorax, both of which have led to wide variations in practice. In addition, most of the published pediatric studies are also limited to small case series.[10] The optimal management of chylothorax is unclear because no prospective studies exist to aide in the choice of therapy since different protocols and strategies are followed in each center.[11,12] The primary modes of treatment include pleural space evacuation, the use of MCT oil-based formulas, enteric rest, and parenteral alimentation,[12,13] and these have shown a success rate of 77% within a maximum of 45 days, with an average time of approximately 12 days.[14] Previous studies have suggested that persistent chylous output for more than three weeks and lesions associated with elevated systemic venous pressure were risk factors for the failure of conservative management options.[1,2,13] Conservative treatment was successful in 15 (83.3%) of our patients, and they were hospitalized for an average of 2.3 weeks. Since we knew that cavopulmonary anastomosis procedures have a higher risk for prolonged pleural drainage, a more aggressive therapy with early initiation might be indicated for these patients;[3] hence, the need for a standard treatment protocol for chylothorax is crucial. Yeh et al.[11] formulated a chylothorax algorhythm treatment in 2013 that produced an early diagnosis which reduced the time in the hospital as well as the use of mechanical ventilation. Their patients were fed with medium chained fatty acids when the amount of drainage was <20 mL/kg/day, but the oral intake ceased when the amount of drainage was >20 mL/kg/day. Then TPN was started, and octreotide therapy of approximately 3 mcg/kg/h was given for a period of between seven and 10 days. In addition, tube ligation, both with and without pleurodesis, was performed in the patients who did not have a decrease in the amount of drainage. We have been applying this modified protocol at our clinic for almost two months now, and thus far, it appears to be practical and useful. However, further studies should be conducted to evaluate whether earlier intervention can reduce the hospitalization times and improve the prognoses.

If conservative therapy fails to control the leak, surgical intervention is advocated, although there is not yet a consensus regarding the specific, precise criteria needed to abandon the conservative therapy. [12] Nevertheless, it is generally accepted that in spite of the use of conservative therapy, if lymphatic leakage persists beyond a few weeks or if massive fluid and nutritional losses present a danger to the patient, then operative intervention is indicated.[12] Some authors have recommended that the surgery take place within five to seven days to limit the morbidity and mortality associated with the operation,[12] but others believe it is better to wait for approximately two weeks or longer in order to provide an adequate time for medical treatment.[8,12] Two surgical strategies predominate: direct wound ligature and en masse supradiaphragmatic ligature. Particularly for our patients with a single ventricle, we treated the postoperative chylothorax aggressively, believing that we should not wait for pleurodesis and ligation. Pleurodesis has been recommended for refractory chylothorax that does not respond to medical or surgical intervention or the fenestration of the diaphragm, and some have also advocated for the creation of pleura-peritoneal windows to treat this condition.[14-16] However, none of our patients required these procedures. The vast majority responded to the use of conservative management or thoracic duct ligation without the need for further interventions that are often necessary in severe refractory cases.

In recent years, there has also been an increase in the use of the somatostatin analogue known as octreotide. It is not yet known how this analogue results in less chylothorax drainage, but it might be associated with a reduction in splanchnic blood flow as well as hepatic venous pressure which results in the decreased movement of the chylous triglyceride content toward the ductus thoracicus. More importantly, no side effects have been reported with octreotide therapy.[17,18] In our study, this therapy was given to 14 patients, but five of these later required pleurodesis or ligation.

The morbidity associated with chylothorax is potentially severe because the large losses of fluids, proteins, lipids, and WBCs can cause dehydration, nutritional deficiency, and immunological dysfunction.[10] In our study, three patients died (8.5%), which was similar to previous studies that had mortality rates of between 6 and 21%.[1,9,12,13] The cause of death in our patients was likely multifactorial due to the unfavorable hemodynamics, sepsis, and multiple organ dysfunction. The most observed complication in our study was septicemia in nine patients. In addition, six had to be reentubated, five developed arrhythmias and pneumothoraces, and four were rehospitalized because of the chylothorax, with two of these being treated with medical therapy, one with pleurodesis, and the other with successful ligation.

Our study had some limitations. It had relatively small sample size and also contained no control group. Furthermore, the cases were reviewed retrospectively, and there was a lack of hemodynamic and laboratory testing of the fluid, especially in the patients who underwent single-ventricle repair.

Conclusion

Chylothorax after pediatric cardiac surgery is not a rare complication. It occurs more commonly after single-ventricle repair and has a significant impact on the postoperative course and morbidity. An accurate diagnosis and early treatment are important to achieve a favorable outcome; therefore, the development of pleural effusion after a cardiothoracic procedure should always raise the suspicion of chylothorax. Surgical intervention should be reserved for the minority of patients who fail to respond to medical treatment, which may be lengthy but can prevent significant morbidity and mortality. While a period of nutritional modifications may be justified, the earlier implementation of octreotide therapy for those with a risk of prolonged chyle loss, such as those with elevated systemic venous pressure, might be beneficial, but prospective randomized controlled trials are needed to confirm the efficacy of this treatment modality.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

References

1) Beghetti M, La Scala G, Belli D, Bugmann P, Kalangos A, Le Coultre C. Etiology and management of pediatric chylothorax. J Pediatr 2000;136:653-8.

2) Büttiker V, Fanconi S, Burger R. Chylothorax in children: guidelines for diagnosis and management. Chest 1999;116:682-7.

3) Chan EH, Russell JL, Williams WG, Van Arsdell GS, Coles JG, McCrindle BW. Postoperative chylothorax after cardiothoracic surgery in children. Ann Thorac Surg 2005;80:1864-70.

4) Mery CM, Moffett BS, Khan MS, Zhang W, Guzmán- Pruneda FA, Fraser CD Jr, et al. Incidence and treatment of chylothorax after cardiac surgery in children: analysis of a large multi-institution database. J Thorac Cardiovasc Surg 2014;147:678-86.

5) Cannizzaro V, Frey B, Bernet-Buettiker V. The role of somatostatin in the treatment of persistent chylothorax in children. Eur J Cardiothorac Surg 2006;30:49-53.

6) Nath DS, Savla J, Khemani RG, Nussbaum DP, Greene CL, Wells WJ. Thoracic duct ligation for persistent chylothorax after pediatric cardiothoracic surgery. Ann Thorac Surg 2009;88:246-51.

7) Jenkins KJ, Gauvreau K, Newburger JW, Spray TL, Moller JH, Iezzoni LI. Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg 2002;123:110-8.

8) Merrigan BA, Winter DC, O'Sullivan GC. Chylothorax. Br J Surg 1997;84:15-20.

9) Allen EM, van Heeckeren DW, Spector ML, Blumer JL. Management of nutritional and infectious complications of postoperative chylothorax in children. J Pediatr Surg 1991;26:1169-74.

10) Ismail SR, Kabbani MS, Najm HK, Shaath GA, Jijeh AM, Hijazi OM. Impact of chylothorax on the early post operative outcome after pediatric cardiovascular surgery. J Saudi Heart Assoc 2014;26:87-92.

11) Yeh J, Brown ER, Kellogg KA, Donohue JE, Yu S, Gaies MG, et al. Utility of a clinical practice guideline in treatment of chylothorax in the postoperative congenital heart patient. Ann Thorac Surg 2013;96:930-6.

12) Milonakis M, Chatzis AC, Giannopoulos NM, Contrafouris C, Bobos D, Kirvassilis GV, et al. Etiology and management of chylothorax following pediatric heart surgery. J Card Surg 2009;24:369-73.

13) Chan SY, Lau W, Wong WH, Cheng LC, Chau AK, Cheung YF. Chylothorax in children after congenital heart surgery. Ann Thorac Surg 2006;82:1650-6.

14) Liu CS, Tsai HL, Chin TW, Wei CF. Surgical treatment of chylothorax caused by cardiothoracic surgery in children. J Chin Med Assoc 2005;68:234-6.

15) Chalret du Rieu M, Baulieux J, Rode A, Mabrut JY. Management of postoperative chylothorax. J Visc Surg 2011;148:346-52.

16) Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32:362-9.

17) Tatar T, Kilic D, Ozkan M, Hatipoglu A, Aslamaci S. Management of chylothorax with octreotide after congenital heart surgery. Thorac Cardiovasc Surg 2011;59:298-301.

18) Tavli V, Yilmazer MM, Guven B, Mese T, Lafci B, Gurbuz A. Octreotide treatment for chylothorax after congenital heart surgery. J Card Surg 2009;24:570-1.