11/29/2017

Chylothorax and other

Lymphatic Flow Disorders:
Etiology and Management

MELANIE SAVOCA, MS, RD, CNSC, LDN

NOVEMBER 14, 2017
The opinions reflected in this Webinar are those of the
speaker and independent of Nutricia North America.

Objectives

1. Understand the anatomy, function and disorders of the lymphatic

system
2. Describe the adverse consequences of lymphatic flow disorders
3. Define the medical nutrition management of lymphatic flow
disorders
4. Discuss a case report and relate learning to one’s own practice

Anatomy of the Lymphatic System

 Complex network of lymphatic vessels throughout the body

 Lymphatic fluid is produced in:
 Soft tissues
 Organs
 Intestines and liver produce the majority (80%) of lymphatic fluid
 Liver is largest producer of lymph and delivers hepatic proteins,
particularly albumin, into bloodstream

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Anatomy of the Lymphatic System

 Lymphatic fluid flows from the organs (liver,

intestines, tissues, lungs) peripherally to
centrally

 Cisterna chyli collect the streams of fluid into

one main channel called the thoracic duct

 The thoracic duct drains into the venous system

through lympho-venous connections at the
junction of the left subclavian and jugular veins

Lymphatic System Function

 Defense
 key role in immune system

 Transport
 cells, fatty acids, proteins, macromolecules

 Circulation
 returns excess interstitial fluid from tissues to venous system

Lymph Fluid

 Chyle
 T cells
 Antithrombin 3 (AT3)
 Proteins
 albumin, fibrinogen, immunoglobulins
 Electrolytes
 Trace elements

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Diagnosis of Chylothorax

 Signs and Symptoms

 Cough, dyspnea
 Nausea and vomiting
 Pleural effusion on chest radiograph

 Thoracentesis
 White, milky or yellow serous fluid
 Biochemical analysis confirmed chylous

What is Chyle?

 Chyle is composed of lymph and emulsified fatty acids as

chylomicrons

 Chyle is formed in the intestinal lacteals during digestion of fat

 Role in absorption of fat soluble vitamins

 Role in reabsorption of proteins lost through capillary leakage

Biochemical Analysis of Chyle

Body Fluid Biochemical Analysis

Triglycerides >110 mg/dL
Total lipid content 0.4-4.0 g/dL
Cholesterol <220 mg/dL
Lymphocytes >70%
White blood cell >1000 per µL
Total protein >3 g/dL
pH Alkaline (7.4-7.8)

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Lymphatic Disorders

 Traumatic Leaks  Idiopathic Leaks

 Chylothorax  Congenital chylothorax
 Chylous ascites  Increased incidence with
Noonan, Turner, and Trisomy 21
 Chylous pericardium
 Trauma, infection, malignancy
 Lymphatic Malformations
 Pulmonary Lymphatic Perfusion
 Lymphoma
Syndrome (PLPS)
 Lymphangiomatosis
 Plastic Bronchitis
 Gorham’s disease
 Protein Losing Enteropathy

Etiology of Chylothorax

 Trauma
 Iatrogenic injury during surgery in the posterior mediastinum
 High risk surgeries: Systemic-to-pulmonary shunts, aortic arch
augmentation, vascular ring repair, delayed chest closure
 Elevated CVP
 Increased pressures cause significant burden on lymphatic circulation and
decreased ability of lymph to drain into the vascular system
 Single ventricle palliation surgeries at increased risk
 Central venous thrombosis
 Presumed mechanism is occlusion of the thoracic duct drainage and
subsequent obstruction of the flow of chyle into venous system

Protein Losing Enteropathy (PLE)

 Condition of the GI tract that results in net loss of proteins

 PLE is characterized by:
 Abnormal enterocyte membrane structure resulting in severe protein loss
into the intestinal tract
 As the protein loss exceeds the patient’s ability to resynthesize the lost
proteins, serum albumin will dramatically decrease
 Decreased absorption of nutrients from the small intestine

Itkin 2017

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Protein Losing Enteropathy (PLE)

 Elevated CVP → overproduction of liver lymph

 Results in dilation of hepatoduodenal lymphatic ducts
and duodenal lacteals
 Liver Lymphangiography
 Documents lymphatic leakage by injecting isosulfan blue dye into
liver lymphatic ducts
 Endoscopy imaging shows subsequent visualization of blue dye
leaking into the duodenal lumen
Dori 2016; Itkin 2017

Protein Losing Enteropathy (PLE)

 Signs and Symptoms

 Abdominal bloating, diarrhea, bowel inflammation, malabsorption
 Hypoalbuminemia, hypoproteinemia
 Ascites, soft tissue swelling, pleural effusions
 Electrolyte disturbances
 Malnutrition secondary to malabsorption

 Diagnosis
 Suspected by history, physical exam, s/s
 Gold Standard: elevated 24 hr stool α-1-antitrypsin clearance study

Adverse Effects of Chylothorax

and Chylous Loss

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Immunological and Hematologic Effects

 Impaired cell-mediated immunity from lymphocyte depletion

 70-90% T cells
 Lymphocytopenia
 Decreased serum levels of antibodies and gamma-globulins

 Increased risk of infection and sepsis

 Increased risk of coagulopathy and thromboembolic events

Electrolyte and Fluid Disturbances

 2 – 4 L/day of chyle are transported through lymphatic system

 Profound losses may cause:
 Electrolyte imbalances (hyponatremia, hypocalcemia, hypokalemia)
 Metabolic acidosis (alkaline pH of chyle)
 Hypovolemia
 Hemodynamic instability
 Hypervolemia
 Inadequate lymphatic drainage or overproduction of lymph leading to
respiratory failure and anasarca
 Secondary to replacement of fluids (FFP, PRBCs, albumin, etc.)

Protein Loss

 Lymph is the only means for protein that has left the vasculature to
be returned to the blood
 Returns ¼ to ½ of circulating plasma proteins
 Hypoproteinemia
 Albumin, fibrinogen, immunoglobulins, enzymes (amylase, lipase, alanine
aminotransferase)

 May have problems maintaining intravascular volume due to

transcapillary fluid shifts

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Fat Soluble Vitamins

 Fat soluble vitamins are transported in chyle

 Additional supplementation may be recommended for patients on a

restricted oral/enteral regimen

 Water soluble forms of vitamins A, D, E and K may be better

utilized with high-output losses or malabsorption

 Laboratory monitoring should be part of a routine nutrition

assessment

Other Adverse Effects

 Respiratory Failure:
 Chylous fluid accumulation in the pleural space can create
restrictive lung disease and contribute to respiratory insufficiency
and need for ventilator support

 Prolonged ICU and hospital admissions

Clinical Nutrition Management

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Management of Chylothorax

 Management is multifactorial
 Conservative therapies are directed to reduce intestinal lymphatic
flow and decrease chyle production through diet modifications
and/or medications
 Registered Dietitians play an integral role in:
 Delivering adequate nutrition for growth and development
 Recommending nutrient supplementation
 Providing nutrition education and counseling

Dietary Management for Chylothorax

 Minimize intake of long-chain triglycerides (LCT)

 Absorbed and transported to the bloodstream by the intestinal lymphatics
as chylomicrons

 Enrich diet with medium-chain triglycerides (MCT)

 Absorbed directly into the portal circulation and do not stimulate an
increase in lymphatic flow

 Oral diet modifications or specialized enteral formula regimens

Postoperative Chylothorax

 Upon diagnosis, a very low fat regimen should be ordered

 Literature recommends a low fat regimen for 4 – 6 weeks after
resolution of chylous drainage
 Once chylothorax has resolved, there is no further preventative
effect of using a restricted diet
 Remaining on a low fat diet longer than necessary is not
nutritionally appropriate and may be harmful in the long-term

Wu 2006, Densupsoontorn 2014, Panthongviriyakul 2008,

Cormack 2004, Cabrera 2010, Beghetti 2000

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Postoperative Chylothorax

 One study measured fat soluble vitamins and fatty acid levels in
patients with CHD who developed chylothorax after cardiac
surgery
 Levels taken at baseline and after 28 days on MCT-rich diet
 Administration of MCT-rich diet for 28 days (range 27-31 days)
was an effective treatment
 Results showed a reduction in vitamin E status and linoleic acid
levels from baseline, but without any symptoms of deficiency

Densupsoontorn 2014

Low Fat Diet

 Estimate ≤10% of EER from fat

 1-10 years of age: ~10-20 grams/day
 >10 years of age: ~15-25 grams/day
 Considerations
 Divide between meals & snacks
 Tolerance to LCT intake is patient specific

 MCT supplementation may enhance energy intake

 MCT oil or MCT modular

Skimmed Breastmilk

 Literature demonstrates safety and efficacy of skimmed breast

milk with the fat removed via centrifugation for the medical
nutrition management of chylothorax in infants
 Content
 Caloric Density: 10–14 cal/oz*
 Fat Content: 0.5%–1.5%*
 Requires addition of calories, protein, MCT and essential fatty acids

 Benefits
 Immunological properties and improved gastrointestinal tolerance
Fogg 2016, *Kocel 2016

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Comparison of Specialized Formulas

High MCT and/or Low LCT Formulas for use of Chylothorax
Formula MCT:LCT Ratio Percent calories from LCT Fat grams
LCT Fat per 100 calories
EnfaportTM 83:17 7.8 0.9 Contains
(Mead Johnson) milk-proteins
Lipistart® 80:20 7.6 0.82
(Néstle)
Monogen® 83:17 4.5 0.5
(Nutricia)
Portagen® 87:13 5.5 0.6
(Mead Johnson)
Tolerex® 0:100 2 0.2 Elemental, 100% free
(Néstle) amino acids
Vivonex® Pediatric 70:30 7.5 0.87
(Néstle)
Vivonex® T.E.N. 0:100 3 0.3
(Néstle)

Nutrition Management

 Parenteral Nutrition
 Fasting decreases intestinal blood flow, which may result
in a secondary reduction in lymph flow
 Aggressive nutrition intervention for malnutrition
 Cannot tolerate restricted enteral fat regimen

 Intralipids are safe

 Delivered directly into the bloodstream
 Do not stimulate lymph production
 Do not pass through the lymphatic system via chyle

Considerations of Restricted Fat Diets

 But…Children need fat/kg/body weight

 Energy requirements
 Growth
 Neurological development
 Long term health
 Prevent essential fatty acid deficiency

Wales et al. Journal of Parenteral and Enteral Nutrition 2014

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Essential Fatty Acids

 EFAs
 Omega-3: α-Linolenic Acid
 Omega-6: Linoleic Acid

 Function
 Formation of phospholipid cellular membranes
 Integrity of epidermal water barrier in the skin
 Development and function of the brain, retina and nervous systems
 Regulate BP, blood viscosity, vasoconstriction
 Role in immune and inflammatory response

Essential Fatty Acid Requirements

Dietary Reference Intakes
 Linoleic acid Adequate Intakes (AI) for EFA
 1–4% of calories Life Stage α-Linolenic Linoleic Acid
Group Acid AI (g/d) AI (g/d)
 α-linolenic acid Infants
 0.2–1% of calories 0-6 months 0.5 4.4
7-12 months 0.5 4.6
 Supplementation Children
 Fish, leafy vegetables, seeds, nuts, 1-3 years 0.7 7
flax, eggs, wheat germ 4-8 years 0.9 10

 Walnut, flax seed, canola, chia seed Males

9-13 years 1.2 12
oils
14-18 years 1.6 16
 Anecdotally, flaxseed oil can Females
increase mucus production and 9-13 years 1.0 10
cause GI side effects 14-18 years 1.1 11

Essential Fatty Acid Deficiency

 Hair loss  Hypertension

 Eczema, dermatitis, folliculitis  Hematologic disturbances
 Growth retardation  hemolytic anemia
 Developmental delay  Fatty infiltrations of the liver
 Xerosis  Hypertriglyceridemia
 Poor wound healing
 Increased susceptibility to infection

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How do we define EFA deficiency?

 Measure absolute serum levels

 Low Linoleic Acid (LA)
 Low α-Linolenic Acid (ALA)
 Elevated Mead Acid
 Elevated Triene:Tetraene (T:T) ratio
 Mild deficiency ≥ 0.05
 Moderate deficiency ≥ 0.2
 Severe deficiency ≥ 0.4

Holman 1960

Vitamin/Mineral Lab Monitoring

 Vitamin 25(OH)D  Check if concern for:

 Vitamin A, E  Suboptimal intake
 Chronic drainage/losses
 Prothrombin times (PTT)
 Zinc  Monitor monthly if abnormal
 Copper  Monitor EFA profile Q 2-4
 Ceruloplasmin months if normal but
remains on a long-term
 Selenium
restricted diet

Nutrition Management of PLE

 No gold standard nutrition recommendations exist

 High-protein (≥2 g/kg/day)
 Reduced LCT, MCT-enriched diet
 Diet modifications may augment a patient’s nutritional intake and
absorption, which may improve morbidity and success of other
medical therapies
 High risk for malnutrition

Johnson 2012

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Neonatal Congenital Chylothorax

 Idiopathic condition that presents as a pleural effusion

inutero or in the early days of life due to the development
of abnormal pulmonary lymphatic flow
 May require prolonged diet modifications with slow
reintroduction of fat as the lymphatic system is immature,
and they have an inability to collateralize until around 8-10
months of age

MR Lymphangiography and Embolization

 Dynamic Contrast Magnetic Resonance Lymphangiography

 Lymphatic system is accessed through lymph nodes and
contrast is injected to determine the anatomy and flow pattern of
lymph in the central lymphatic system

 Lymphatic Embolization
 Under fluoroscopic guidance, a needle is inserted percutaneously
through the abdomen into the cisterna chyli
 Guidewire and microcatheter are advanced into the thoracic duct
 Injection of lipiodol occludes the pathologic lymphatic network and
supplying vessels

Other Considerations and Challenges

 Coagulation
 Pain
 Illness-associated anorexia
 Malnutrition
 Fluid management
 Wound care
 Child life/psych

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Case Study

Case Study

 DW is a female with a PMH of hypoplastic left heart syndrome, interrupted IVC

and azygous continuation to the left SVC, and heterotaxy syndrome. She
initially had a Stage 1 palliation with BT shunt after birth, followed by a
Kawashima operation. She subsequently developed pulmonary arteriovenous
malformations, and underwent a Fontan with hepatic inclusion at 17 months
old and was discharged home.

 At 18 months of age, she presented with left chylous pleural effusion. She
underwent cardiac cath, thoracentesis, and left pleural pigtail catheter.

 Diet History: Regular diet and breast milk, although weaning

Case Study

Body Fluid Composition  Drainage day 1-10:

Type of Body Fluid Pleural  Avg 341 mL/day (32 mL/kg/day)
Appearance Cloudy  Range 220-700 mL/day
Fluid Color Yellow
 Lab Abnormalities:
Lymphocytes 91 %
 Na 139 → 133 (L)
Total Protein 3.5 g/dL
 Albumin 3.9 → 2.9 (L)
Triglyceride 225 mg/dL
White blood cells 2128 /µL

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Case Study

 Nutrition Assessment
 EER: 100-110 kcal/kg @ 10.5 kg = 1050-1150 kcal/day

 Anthropometrics: well nourished on admission

 Nutrition concerns: intermittent nausea, poor appetite

Case Study

 Nutrition Intervention
 Ordered for a low fat diet
 10% EER from fat = 11-13 grams fat/day

 She was eating fruits, starches, fat free dairy products, small
amount of lean meats
 Ordered for Monogen® with DHA & ARA 30 cal/oz
 Drinking ~16 ounces per day (~2.2 g LCT)

 Drainage gradually slowed and CT removed after 20 days

Case Study

 Discharged home after 3 week admission with plan to

continue the low fat regimen given concern for underlying
lymphatic abnormality
 Mom continued to express fear of giving oral fat; may likely
be receiving <10 g/day by mouth
 After 8 weeks of remaining on a low fat regimen, EFA
profile and zinc levels were checked

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Case Study

 Essential Fatty Acid Profile after 8 weeks on low-fat diet

Result Reference Range
α-Linolenic acid 35 20–200 nmol/mL
Linoleic acid 1211 1210–4300 nmol/mL
Mead Acid 164 (H) 1–35 nmol/mL
Triene:Tetraene ratio 0.427 (H) 0.004–0.05
Zinc 74 60–120 mcg/dL

 Labs notable for severe EFA deficiency for which EFA supplementation
with walnut and flaxseed oil was started
 Educated parents on optimizing EFA intake in the diet

Case Study

 Learning points:
 Increased deficiency risk after 4 weeks on a restricted diet
 Close nutrition laboratory monitoring is imperative
 Preventative supplementation may be beneficial when EFA and
micronutrient intake is suboptimal
 Parental education is vital to help understand diet modifications,
risks, and importance of supplementation

Summary

 Lymphatic system is vital for immunity and transport of

protein, fat, and fluid
 Conservative management of chylothorax is with diet
modifications
 Children are at high risk for protein-calorie malnutrition,
essential fatty acid and other micronutrient deficiencies
 Further research is needed to better define nutrition
recommendations for other lymphatic disorders

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Disclaimer

 Any specific brands mentioned are examples or

recommendations of this healthcare professional and,
aside from those which specify they are manufactured by
Nutricia, are not affiliated with or endorsed by Nutricia.

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References

 Dori Y. Novel lymphatic imaging techniques. Tech Vasc Interv Radiol. 2016;19(4):255-261.
 Hsu MC, Itkin M. Lymphatic anatomy. Tech Vasc Interv Radiol. 2016;19(4):247-254.
 Loukas M, Bellary SS, Kuklinski M, et al. The lymphatic system: a historical perspective. Clin
Anat. 2011;24(7):807-816.
 Biewer ES, Zürn C, Arnold R, et al. Chylothorax after surgery on congenital heart disease
in newborns and infants: risk factors and efficacy of MCT-diet. Journal of Cardiothoracic
Surgery. 2010;5:127.
 Dori Y, Keller MS, Rome JJ, et al. Percutaneous Lymphatic Embolization of Abnormal
Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital
Heart Disease. Circulation. 2016;133:1160-1170.
 Zuluaga MT. Chylothorax after surgery for congenital heart disease. Curr Opin
Pediatr. 2012;24(3):291-294.

References

 Itkin M, Piccoli DA, Nadolski G, Rychik J, DeWitt A, Pinto E, Rome J, Dori Y. Protein-Losing
Enteropathy in Patients With Congenital Heart Disease. J Am Coll Cardiol. 2017;69(24):2929-
2937.
 Chavhan GB, Amaral JG, Temple M, Itkin M. MR Lymphangiography in Children: Technique
and Potential Applications. Radiographics. 2017;37(6):1775-1790.
 Attar MA, Donn SM. Congenital chylothorax. Semin Fetal Neonatal Med. 2017;22(4):234-239.
 Holman RT. The ratio of trienoic: tetraenoic acids in tissue lipids as a measure of essential
fatty acid requirement. J Nutr. 1960;70:405-410.
 Sardesai VM. The essential fatty acids. Nutr Clin Pract. 1992;7(4):179–186.
 Itkin M. Interventional treatment of pulmonary lymphatic anomalies. Tech Vasc Interv Radiol.
2016;19(4):299-304.
 Asbagh PA, Navabi Shirazi MA, Soleimani A, et al. Incidence and Etiology of Chylothorax after
Congenital Heart Surgery in Children. J Tehran Heart Cent. 2014; 9(2): 59–63.

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