Download Chylothorax in Infants and Children abstract

Chylothorax in Infants and Children
abstract
Chylothorax, the accumulation of chyle in the pleural space, is a relatively rare cause of pleural effusion in children. It can cause significant respiratory morbidity, as well as lead to malnutrition and
immunodeficiency. Thus, a chylothorax requires timely diagnosis
and treatment. This review will first discuss the anatomy and physiology of the lymphatic system and discuss various causes that can
lead to development of a chylothorax in infants and children. Then,
methods of diagnosis and treatment will be reviewed. Finally, complications of chylothorax will be reviewed. Pediatrics 2014;133:722–733
AUTHOR: James D. Tutor, MD
Program in Pediatric Pulmonary Medicine, University of
Tennessee Health Science Center; Le Bonheur Children’s Hospital;
and St. Jude Children’s Research Hospital, Memphis, Tennessee
KEY WORDS
chylothorax, infants, children
www.pediatrics.org/cgi/doi/10.1542/peds.2013-2072
doi:10.1542/peds.2013-2072
Accepted for publication Oct 2, 2013
Address correspondence to James D. Tutor, MD, Division of
Pulmonology, Department of Pediatrics, Le Bonheur Children’s
Hospital, 50 North Dunlap St, Memphis, TN 38103. E-mail:
[email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2014 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The author has indicated he has no
financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The author has indicated he
has no potential conflicts of interest to disclose.
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TUTOR
STATE-OF-THE-ART REVIEW ARTICLE
Chylothorax, the accumulation of chyle
in the pleural space, occurs after disruption of the thoracic duct.1 The incidence of chylothorax in children is
unknown. Although a rare cause of
pleural effusion in most children,2 it is
the most common form of pleural effusion in neonates.3 It can result in
significant respiratory morbidity and
immunodeficiency in infants and children if not diagnosed and treated.
Here, the anatomy and physiology of
the lymphatic system will be reviewed, as well as some of the various
causes of chylothorax in infants and
children. Current methods of diagnosis and management, and some
associated complications, will be
reviewed.
ANATOMY AND PHYSIOLOGY OF
THE LYMPHATIC SYSTEM
The human lymphatic system has 3
main functions: (1) transport lipids and
lipid-soluble vitamins to the systemic
circulation; (2) collect and return excess fluid and extravasated proteins
from the interstitial spaces to the circulation; and (3) return lymphocytes to
the circulation.1,2
From the lacteals, the chyle is transported to the cisterna chyli, which
overlies the anterior surface of the
second lumbar vertebra.4 The duct
passes through the esophageal hiatus
of the diaphragm into the thoracic
cavity, ascends extrapleurally in the
posterior mediastinum to the right of
the vertebral column, and lies between
the azygous vein and the descending
aorta, in close proximity to the esophagus and the pericardium. At the fourth
to sixth thoracic vertebrae, the duct
crosses to the left of the vertebral
column and continues cephalic to enter the superior mediastinum between
the aortic arch and the subclavian artery and the left side of the esophagus.
Once past the thoracic inlet, it arches 3
to 5 cm above the clavicle and passes
PEDIATRICS Volume 133, Number 4, April 2014
anterior to the subclavian artery, vertebral artery, and thyrocervical trunk
to terminate near the left jugular and
subclavian veins.1 Many anatomic variations can exist in all portions of the
thoracic duct.5,6
Chyle is a noninflammatory, alkaline,
and bacteriostatic fluid composed
mainly of fat, cholesterol, electrolytes,
proteins, glucose, and abundant lymphocytes (Table 1).2 The protein content
of chyle is usually .3 g/L, and the
electrolyte composition is similar to
that of serum.7 The lymphocyte count
ranges from 400 to 6800/mm3, with
most being T lymphocytes.8 Chyle appears as a milky, opalescent fluid that
separates into 3 layers upon standing:
a creamy uppermost layer containing
chylomicrons, a milky intermediate
layer, and a dependent layer containing
cellular elements, most of which are
small lymphocytes.9 Chyle may be
slightly turbid if an individual has not
eaten recently because its lipid content
will be reduced.1 The thoracic duct
transports between 1.5 and 2.5 L of
chyle daily (maximum 4 L/day in
a healthy adult). Flow varies depending
on the diet, medications, intestinal
function, and physical activity, and it
can increase by two- to 10-fold for 2 to 3
TABLE 1 Components of Chyle2,108
Component
Amount
pH
Absolute cell count
Lymphocytes
Erythrocytes
Calories
Total fat
Cholesterol
Triglycerides
7.4–7.8
.1000 cells/L
400–6800/mm3
50–600/mm3
200 kcal/L
0.4–0.6 g/dL
65–220 mg/dL
. 110 mg/dL
(.1.1 mmol/L)
Present
2–6 g/dL
1.2–4.1 g/dL
1.1–3.1 g/dL
2.7–11 mmol/L
104–108 mmol/L
3.8–5.0 mmol/L
85–130 mmol/L
3.4–6.0 mmol/L
0.8–4.2 mmol/L
Chylomicrons
Total protein
Albumin
Globulin
Glucose
Sodium
Potassium
Chloride
Calcium
Phosphate
hours after ingestion of fat, and by 20%
after drinking water.2,7
CAUSES OF CHYLOTHORAX
There are several causes of chylothorax
in infants and children (Table 2), which
vary according to the age of the child or
mechanism of injury to the thoracic
TABLE 2 Causes of Chylothorax in Children
I. Congenital chylothorax
A. Congenital lymphatic malformations
1. Lymphangiomatosis
2. Lymphangiectasia
3. Atresia of thoracic duct.
B. Associated with syndromes
1. Down syndrome
2. Noonan syndrome
3. Turner syndrome
4. Gorham-Stout syndrome
5. X-linked myotubular myopathy
6. Missense mutation in integrin a9b1
7. Hydrops fetalis
8. Yellow nail syndrome
II. Traumatic
A. Associated with surgeries for
1. Excision of lymph nodes
2. Congenital heart disease
3. Scoliosis
4. Vascular ring
5. Diaphragmatic hernia
B. Invasive diagnostic and therapeutic
procedures
1. Subclavian vein catheterization
C. Other trauma
1. Blunt force or penetrating trauma to the
chest
2. Hyperexpansion or stretching of chest wall
or thoracic spine
3. Coughing
4. Vomiting
5. Child birth
6. Child abuse
III. High central venous pressure
A. Thrombosis of superior vena cava
B. Post-Fontan surgery
IV. Associated with tumors
A. Neurogenic
B. Lymphoma
C. Teratoma
D. Wilms
E. Ovarian
F. Kaposi sarcoma
V. Miscellaneous
A. Granulomatous infections
1. Tuberculosis
2. Histoplasmosis
3. Sarcoidosis
B. Other
1. Staphylococcal discitis
2. Henoch-Schönlein purpura
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duct. It may result from congenital
abnormalities of the lymphatics, which
do not always present in the neonatal
period.2
Pulmonary lymphangiomas and lymphangiectasia are the 2 major lymphatic abnormalities associated with
chylothorax,2 but absence or atresia of
the thoracic duct can also lead to this
problem.10 Pulmonary lymphangiomatosis is a focal proliferation of well
differentiated lymphatic tissues often
associated with lymphatic abnormalities in other organs, whereas pulmonary lymphangiectasia is diffuse
dilatation of the interlobular and subpleural lymphatics.2 Lymphangiomas
usually present by 2 years of age, but
they may not be recognized until
adulthood. If they occur in the head,
neck, or axial skeleton, they can extend
into the mediastinum. About 1% of
lymphangiomas are confined to the
chest.2 Lymphangiectasia can be a primary condition that is often fatal in
newborns, or it can be secondary to
other conditions, such as congenital
heart disease or pulmonary venous
obstruction, where there is abnormal
drainage or an increase in lymph production.2 Diagnosis of pulmonary lymphangiomatosis and lymphangiectasia
can be made by lymphoscintigraphy,11
computerized tomography,12 or MRI.13
Lung biopsy is often necessary for
confirmation.14,15 Lymphangiomas are
treated with surgical excision or sclerotherapy.14 There are reports of the successful use of radiotherapy for cases
in which chylothorax was refractory to
surgical management.16,17
Chylothorax can be a manifestation of
Down,18–21 Turner,18–20 and Noonan
syndromes.18–20,22–24 Congenital and
pulmonary lymphangiectasia occur
in these syndromes.2 Other syndromes
associated with chylothorax are X-linked
myotubular myopathy,25 missense mutation in integrin a9b1,26,27 and GorhamStout syndrome.28–34 Members of the
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integrin family of adhesion receptors
mediate both cell–cell and cell–matrix
interactions and have been shown
to play vital roles in embryonic development, wound healing, and other
biologic processes. Gorham-Stout disease, characterized by proliferation of
vascular structures within bones,
leads to osteolytic lesions evident
on radiography. It has no known inheritance pattern. Chylothorax is associated with the disease, possibly
related to dysplasia of lymphatic vessels at the pleura. Children are more
commonly affected than adults, and
presenting symptoms may include
cough, dyspnea, and pain. The presence of chylothorax is associated with
worsened prognosis.35 Anecdotal reports suggest that interferon a2b may
be trialed in the treatment of this
disease.31,35 Chylothorax can occur in
the presence of hydrops fetalis.36,37 It
has been seen in a newborn infant
with nonimmune hydrops fetalis and
yellow nail syndrome.38
abuse, such as heavy blows to the back
or stomach, can cause rupture of the
thoracic duct, leading to the development of chylothorax.64–66 Chylothorax due to closed trauma is usually
on the right side, with the site of rupture most commonly in the region of
the ninth or 10th thoracic vertebra.67
Trauma can cause chylothorax by rupture or laceration of the thoracic duct.2
It occurs as a postoperative complication after various surgeries involving
structures in the neck and thorax.39–44
Other surgeries that can be complicated
by chylothorax in children include those
for treatment of scoliosis,45–48 vascular
rings,49,50 and diaphragmatic hernia.51
In children, the reported incidence of
chylothorax after cardiothoracic surgery is between 0.85% and 6.6%.39,52–54
Another traumatic cause of chylothorax
is laceration of the thoracic duct during catheterization of the subclavian
vein.55,56
Granulomatous infections such as tuberculosis,81–83 histoplasmosis,84 and
sarcoidosis85 can be associated with
the development of chylothorax attributable to lymphadenopathy obstructing the thoracic duct. Other etiologies
include staphylococcal discitis86 and
Henoch-Schönlein purpura.87
Noniatrogenic trauma can lead to the
development of chylothorax. These include blunt force or penetrating trauma
to the chest,57–61 sudden hyperextension, or stretching of the chest wall or
thoracic spine with fracture of a vertebra,2 severe coughing or vomiting,62
and the force of child birth.2,63 Child
Venous thrombus or obstruction in the
superior vena cava or subclavian vein
may lead to rupture of the thoracic
duct.55,56,68 Chylothorax can complicate
innominate vein69 or left subclavian
vein thrombosis70 and the Fontan procedure.71–73
Chylothorax can be associated with
various tumors and malignancies
(neurogenic,74,75 lymphoma,2 teratoma,2
Wilms,76 ovarian,77 and Kaposi sarcoma78).
Lymphoma is the most common tumor
associated with chylothorax (60% to
70% of cases),2 and it may be the presenting symptom.7,79,80 The presence
of a nontraumatic chylothorax is an
indication for a diligent search for a
lymphoma.1
CLINICAL MANIFESTATIONS OF
CHYLOTHORAX
The initial symptoms of chylothorax are
usually related to accumulation of fluid
in the pleural space.1,2 Patients can
be asymptomatic; however, dyspnea,
cough, and chest discomfort develop
with time.2 Pleuritic chest pain and fever are rare.1 With traumatic chylothorax, a latent period of 2 to 10 days
usually occurs between the trauma
and the onset of the pleural effusion.67
Lymph collects extrapleurally in the
mediastinum after the thoracic duct
STATE-OF-THE-ART REVIEW ARTICLE
disruption, forms a chyloma, and produces a posterior mediastinal mass.6
The mediastinal pleura ruptures, chyle
gains access to the pleural space, and
dyspnea is produced by the chyle
compressing the lung.1 Rapid accumulation of a large volume of fluid can
lead to adverse hemodynamic complications with significant cardiorespiratory difficulties, such as hypotension,
cyanosis, and significant respiratory
distress.1,2 In patients with nontraumatic chylothorax, symptom onset
is gradual.1 Congenital chylothorax
presenting antenatally can act as
a space-occupying lesion and restrict
normal development of the lungs.2 At
birth, the infant develops respiratory
distress; 50% of patients have symptoms within the first 24 hours, whereas
75% have symptoms by the end of the
first week.88 On physical examination,
there is bilateral or unilateral dullness
to percussion, and poor air entry.89
Among patients with chronic chylothorax, muscle wasting, weight loss,
and other signs of malnutrition can be
present.1 The patients may be compromised immunologically because
of lymphocyte depletion and hypogammaglobulinemia.1,14
DIAGNOSIS OF CHYLOTHORAX
A chest radiograph can reveal pleural
fluid and assess the size and location of
the effusion. Use of lateral decubitus
radiographs or ultrasound can determine whether there is free fluid in
the pleural space or whether it is organized.90
Chyle obtained on thoracentesis is
white, odorless, and milky in appearance. When this type of fluid is obtained,
the differentiation is between empyema
and pseudochylothorax with a chyliform
pleural effusion. A pseudochylothorax
is a long-standing (mean 5 years)
pleural effusion that is turbid or milky,
containing large amounts of cholesterol
or lecithin-globulin complexes (chyliform).
PEDIATRICS Volume 133, Number 4, April 2014
It does not result from disruption of the
thoracic duct.1 The visceral pleura in
a pseudochylothorax is thickened and
may be calcified, whereas with chylothorax there is acute onset and the
pleural surfaces are normal.91 The
milkiness of the fluid from an empyema
is caused by suspended white blood
cells. If the fluid is centrifuged, the
supernatant will be clear. Chylous and
chyliform pleural fluids remain opaque
after centrifugation. If cholesterol
crystals are responsible for the turbidity, they may be easily demonstrated
by examination of the pleural fluid
sediment.1 If the turbidity is because of
high levels of cholesterol, it will clear
with the addition of 1 to 2 mL ethyl
ether. If it is due to chylomicrons or
lecithin complexes, the fluid will not
clear.92
The best way to diagnose chylothorax is
by measuring the triglyceride and
cholesterol levels in the pleural fluid.1 If
the triglyceride level is above 110 mg/
dL and the ratio of the pleural fluid to
serum cholesterol is ,1.0, the diagnosis is established. In a pseudochylothorax, the ratio will exceed 1.0.93 If
there is still doubt about whether the
pleural effusion is a chylothorax or
a pseudochylothorax, the fluid should
be analyzed for chylomicrons by lipoprotein analysis. Demonstration of
chylomicrons confirms the diagnosis
of chylothorax.94 With congenital chylothorax, the pleural fluid is serous and
becomes chylous when milk feedings
are started.88 Pleural fluid triglyceride
and lipoprotein analysis should be
performed in all newborns with pleural
effusion.1,88
OTHER INVESTIGATIONS
Once chylothorax has been diagnosed,
other radiologic studies will likely be
needed to further investigate the lymphatic system. Studies to outline the
lymphatic vessels, identify the site of
chyle leakage, and determine the cause
of the chylothorax should be performed.
Imaging studies such as computerized
tomography scans, lymphangiography,
and lymphoscintigraphy can be helpful.2 Occasionally, MRI is used, particularly if the mediastinum needs to be
imaged.2
Lymphangiography and lymphoscintigraphy both require the administration
of a contrast agent. This can be done by
interstitial (intradermal or subcutaneous)
administration, administration into a cannulated lymphatic vessel, intravenous injection, or injection into a lymph node.95–97
Lymphangiography implies the administration of an iodinated contrast agent
into a cannulated lymph vessel. A simultaneous chest radiograph or computerized tomography scan will delineate the
lymphatic anatomy. The sensitivity of
lymphangiography can be low because
it is difficult to visualize the entire
length of the thoracic duct because of
poor mixing of oily contrast medium
and chyle.2 Successful identification
rates of up to 81% have been reported
in adults.98 Limitations include the technical skills needed to cannulate lymph
vessels, pain, infection, respiratory distress, and damage to the lymphatics.2
Thus, many medical centers no longer
perform lymphangiograms.1 An alternative is lymphoscintigraphy, a faster
and less traumatic nuclear imaging
technique that utilizes filtered 99mTc injected intradermally or subcutaneously
as a contrast agent.2,99
Computerized tomography can be
useful to image the mediastinum, especially if nontraumatic chylothorax is
suspected, and can detect small amounts
of contrast material in the pleural space.2
It has been used in at least 1 case to aid
in the diagnosis of lymphangiomatosis
in a child.12
Magnetic resonance lymphography
involves interstitial or intravenous injection of gadolinium-based contrast
agents. This technique has been used
in adults with good delineation of
725
lymphatic vessels.100,101 MRI has been
used in at least 1 case of disseminated
lymphangiomatosis in a child to help
assess the extent of the disease.13
If direct visualization of a chyle leak
point is needed, thoracoscopy can be
useful. It also allows for biopsies of any
suspect areas.2
MEDICAL MANAGEMENT OF
CHYLOTHORAX
The goals of management of chylothorax are relief of respiratory symptoms by drainage of the pleural fluid,
prevention of recurrence by treatment of the underlying cause, and
prevention/treatment of malnutrition
and immunodeficiency (Fig 1).
The initial step is aspiration of the
pleural fluid for diagnostic purposes. If
the effusion is large and compromising
respiration, or if the effusion is likely to
reoccur, then a chest tube should be
inserted for continuous drainage of the
pleural space. Quantification of drainage
is useful to guide treatment of fluid
imbalances.2 Some centers use daily
drainage as a guide for clinical improvement or failure (,10 mL/kg per
day of pleural drainage is considered
to be an improvement; .10 mL/kg per
day of pleural drainage is considered
to be a failure after 4 weeks of nonsurgical management).52 In severely ill
patients, assisted ventilation may be
necessary. The use of positive endexpiratory pressure ventilation may
tamponade the injured duct, helping
to decrease chyle flow.102–104 There is
1 report of the successful use of highfrequency oscillatory ventilation in
severely ill neonates with congenital
chylothoraces.105
There are several nonsurgical methods
(dietary modifications and/or adjunctive medications) that have been used to
try to prevent or treat chylothorax
reoccurrence if the leak does not
spontaneously resolve. Most series
performed in children recommend up
to a 2- to 4-week trial of nonsurgical
FIGURE 1
Algorithm for evaluation and treatment of chylothorax in children.
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therapies before surgery is considered.2 Nonoperative management of
chylothorax in children is successful in
.80% of reported cases, including
those patients with chylothorax after
cardiothoracic surgery.5,39,52–54,106,107
To reduce the flow of chyle through the
thoracic duct while waiting for spontaneous healing to occur, a fat-free diet
with the addition of medium-chain triglycerides is instituted. Medium-chain
triglycerides with saturated fatty acids
of 8 to 12 carbon chain lengths are
absorbed directly into the portal venous system, bypassing lymphatic
drainage.2 Several enteral formulas
are available commercially that contain a high percentage of mediumchain triglycerides but also contain
some long-chain fatty acids as well:
Optimental (Abbott Nutrition, Columbus,
OH), Peptamen (Nestle Health Science,
Vevey, Switzerland), Peptamen AF (Nestle
Health Science), Peptamen 1.5 (Nestle
Health Science), Perative (Abbott Nutrition), Portagen (Mead Johnson Nutrition,
STATE-OF-THE-ART REVIEW ARTICLE
Glenview, IL), Monagen (Nutricia,
Gaithersburg, MD), Enfaport (Mead
Johnson Nutrition), Pregestimil (Mead
Johnson Nutrition), Vital HN (Abbott
Nutrition), Vital HN 1.5 (Abbott Nutrition), and Vivonex TEN (Nestle Health
Science). Medium-chain triglyceride
formulas do not contain essential fatty
acids, so those will need to be supplemented if these formulas are used for
.3 weeks.108 There is a report of the
successful use of an enteral formula
containing long-chain triglycerides,109
and a report of the combined use of
low-fat breast milk and octreotide, to
treat postoperative chylothorax.110 A
more aggressive option is complete
enteric rest by using total parenteral
nutrition.54 There are several intravenous lipid emulsions that are designed to be delivered directly into the
blood stream: Intralipid and Liposyn.
They do not travel through the lymph
system and do not contribute to chyle
flow. They also provide essential fatty
acids. In adults, enteral nutrition may
be effective if chyle output is ,1000
mL/day. A low fat semielemental formula may be effective if chyle output is
,500 mL/day. An elemental formula
may be required if chyle output is .500
mL/day. Parenteral nutrition will be
required if chyle output is .1000 mL/
day in adults, or if patients are not
responding to a modified oral or enteral regimen, or if they are having
increased chyle output on enteral
nutrition.108 Whether enteral or parenteral nutrition is chosen, the calories, electrolytes, and volume must at
least match those lost in the chyle
output. In a group of 51 children with
chylothorax, the use of conservative
enteral or parenteral therapy for 1
to 3 weeks resulted in resolution of
the chylothorax in 41 (80%) of the
children.52
Somatostatin is an endogenous hormone with actions that include effects
on the gastrointestinal tract. Octreotide
PEDIATRICS Volume 133, Number 4, April 2014
is a synthetic, long-acting somatostatin
analog. These agents, whose mechanism(s) of action is(are) not clear, have
been used in the management of chylothorax with varying results.2 It may be
that they cause a reduction in intestinal
blood flow by vasoconstriction of the
splanchnic circulation, with reduction
of lymphatic fluid production.111,112 Alternately, the lymphatic vessels may
have somatostatin receptors, and their
stimulation could result in decreased
lymphatic flow.113 These agents also
decrease gastrointestinal motility, and
decrease the volume of gastric, pancreatic, and biliary secretions, which
in turn decreases lymphatic flow.114–116
In comparison with somatostatin,
octreotide has a longer half-life, greater
potency, and the option of subcutaneous
administration.115,116 Either drug can be
given as a continuous intravenous infusion or as an intravenous bolus twice
daily. The starting dose of somatostatin
is 3.5 mg/kg per hour, which can be increased to 10 mg/kg per hour.111 The
dose for octreotide in children has
ranged from 0.3 to 1.0 mg/kg per
hour.117,118 The optimal timing of introduction and duration of treatment is
unknown.2 Side effects of somatostatin
and octreotide include hyperglycemia,
hypothyroidism,119 cramps, nausea, diarrhea, renal impairment, necrotizing
enterocolitis,120 and liver dysfunction.115,116
A case of anaphylaxis has been reported in a child after the use of octreotide.121 Shah and Sinn122 reported the
use of octreotide in 6 patients with
congenital chylothorax by using a dose
range of 0.5 to 10 mg/kg per hour.
Octreotide was started at a median age
of 13.5 days (range, 8 to 22 days) and
was given for a median of 20 days
(range, 12 to 27 days). Five of the 6
patients had resolution of their chylothoraces with this therapy. Roehr
et al116 performed a systematic literature review of the use of somatostatin
and octreotide in 35 children with primary or secondary chylothorax. Most
studies reported a significant decrease in chylous drainage within 5
to 6 days of starting octreotide or somatostatin. A 2010 Cochrane report123
described the use of octreotide in 20
neonates with chylothorax. Fourteen of
the case reports described successful
resolution of chylothorax, 4 reported
no resolution, and 1 reported equivocal
results. No practice recommendation
was made based on this evidence.
Horvers et al124 reported on the use of
octreotide in 7 patients with congenital
chylothorax. Pleural effusions eventually decreased in all patients after administration of 5 to 6 mg octreotide/kg
per minute, but the authors felt that the
decrease might reflect the natural
history of congenital chylothorax and,
hence, no clear, consistent effect of
octreotide was identified. They noted
that pulmonary hypertension was a
common problem in the patient group.
A randomized, controlled, multicenter
trial is needed to assess the safety and
efficacy of octreotide and somatostatin
use in the treatment of chylothorax in
children.123,124
Other agents used in the treatment of
chylothorax include nitric oxide and
etilefrine. A case report described the
use of nitric oxide in a neonate who
developed a chylothorax after surgery
for congenital heart disease.125 At an
inhaled nitric oxide dose of 20 ppm, the
chest tube drainage markedly decreased and finally ceased 8 days later.
Nitric oxide was discontinued 19 days
after initiation with no recurrence of
the chylothorax. The authors proposed
that functional venous obstruction due
to the patient’s moderate pulmonary
hypertension was a contributor to the
persistence of the chylous leak. The
nitric oxide caused a decrease in pulmonary artery pressure and decreased
systemic venous pressures by augmenting forward flow through the right
side of the heart. Etilefrine is a sympathomimetic drug that has been used
727
in a small number of adults for the
management of postoperative chylothorax with no side effects. It causes
systemic smooth muscle contraction
and is thought to decrease chyle flow
by constriction of the thoracic duct.126,127
SURGICAL MANAGEMENT OF
CHYLOTHORAX
Surgery should be considered when
medical management of chylothorax
has failed to reduce chyle flow and allow
healing of the duct. There is no consensus on the timing of surgery.2 Some
recommend surgery if the effusion
persists for more than 2 weeks. Others
regard a particular volume, such as
.100 mL per year of age in children, as
an indication for surgery.128–130 Most
recommend an extended period (3 to 4
weeks) of conservative management
before proceeding to surgical treatment.52,106 If there is a well identified
site of chyle leak and high flow that
precludes spontaneous healing, a case
for earlier surgery can be made.131
Successful surgery can shorten hospitalization and reduce the risks of
malnutrition and immunosuppression.2
There are several procedures that can
be used for the treatment of chylothorax. If the site of rupture of the
thoracic duct can be identified by
lymphangiography, direct surgical ligation of the duct represents a definitive treatment of chylothorax.9,52,132
Thoracoscopy has a low rate of complications and is cost-effective.133,134
Pego-Fernandez et al134 performed
thoracic duct ligation via thoracoscopy
in 14 children with chylothorax after
cardiac surgery and reported that it
was successful in 12 (86%). Nath
et al132 performed duct ligation in 20
pediatric patients with chylothorax after cardiothoracic surgery. They were
successful in 16 patients (80%), but
noted that patients with thrombus of
upper body venous vessels or prolonged
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chest tube drainage were more likely
to fail and/or die. They recommended
that duct ligation be done within 2
weeks of recognizing the chylothorax. If
needed to visualize the thoracic duct
and the site of leakage during surgery,
the patient can be given a 200-mL
mixture of milk and cream a few hours
before surgery, or an intraoperative
injection of 1% Evans blue dye.131,135,136
If the site of leakage cannot be identified, a mass ligation of the thoracic
duct and its surrounding tissue is done
around the aorta, azygos vein, and
esophagus, adjacent to the vertebral
body,137 or by ligation of the cistern
chyli.138
Another procedure used to manage
chylothorax is obliteration of the pleural
space, either chemically or surgically.
Various agents, such as tetracycline,
talc, bleomycin, fibrin glue, and
povidone-iodine, have been used.139–143
Povidone-iodine 10% dermique diluted
with saline or povidone-iodine 4%
scrub was instilled directly through
a chest tube into the pleural space in
a group of 4 neonates with chylothoraces. Systemic analgesia was
achieved with a morphinomimetic
(fentanyl or sufentanil), and sedation
was provided with intravenous
midazolam. Thyroid function was reported to be normal before and after
instillation of povidone-iodine in 3 of
the infants; it was not checked in the
fourth infant.139 The intrapleural administration of talc can lead to the
development of the acute respiratory
distress syndrome.1 OK-432, an inactive
preparation of Streptococcus pyogenes,
has also been used as an effective
sclerosing agent in neonates.144,145 OK432-induced pleurodesis has been
used as an antenatal treatment of
severe chylothorax associated with
nonimmunologic hydrops fetalis.146,147
Pleurodesis is performed with thoracoscopy, although the sclerosing agent can
be instilled through a chest tube.
Pleurodesis has effectively been used
in cases where medical therapies for
chylothorax failed and direct surgical
duct ligation was not performed.148
A third surgical method to manage
chylothorax is the placement of a pleuroperitoneal shunt. This provides a way
of draining chyle from the pleural space
without losing the fluid. The shunts are
a 1-way subcutaneous connection between the pleura and the peritoneum
that can be inserted with local anesthesia.1,2 They have been used in children whose chylothoraces have been
refractory to treatment with dietary
management, thoracentesis, or tube
thoracostomy, and are reported to be
75% to 90% effective.129,149–151 After
a shunt is implanted, the lymphatic
defect closes spontaneously in most
cases and the shunt can be removed 30
to 90 days after insertion.149 Murphy
et al129 recommended placing the
shunt if drainage from the chylothorax
persisted beyond 5 days. Shunts have
also been used to treat chylothoraces
in preterm infants and in fetuses.37,151
There are case reports of 2 other separate methods that have been used to
manage chylothorax. Fluoroscopically
guided percutaneous embolization of
the thoracic duct has been used to
manage chylothorax.152,153 There are
also reports of autoinfusion of chylothorax fluid in patients who were undergoing hemodialysis.154,155
COMPLICATIONS OF CHYLOTHORAX
Several complications can occur in
association with the development of
chylothorax. These include malnutrition, hyponatremia, fluid imbalance,
respiratory distress, increased risk of
thrombosis,156 and secondary immunodeficiency.2 In 1 reported case of
selenium deficiency because of loss of
selenium in chylous fluid, myopathy
associated with severe cardiomyopathy developed.157
STATE-OF-THE-ART REVIEW ARTICLE
Chylothorax leads to hypogammaglobulinemia and lymphopenia.158–162 In 16
children who developed chylothoraces
after cardiac surgery, there were
decreases in the absolute numbers of
B lymphocytes (CD19+), T lymphocytes
(CD3+), helper T-cells (CD4+), and
suppressor/cytotoxic T-cells (CD8+),
but a normal CD4+:CD8+ ratio.159 The
absolute number of natural killer cells
(CD16+) and metabolic activity of
polymorphonuclear leukocytes was
normal. In another study of 5 children
with chylothorax, 2 had reduced absolute numbers and percentage of CD3+
T-lymphocytes, and all the children had
decreased numbers and percentage of
CD4+ T-lymphocytes.158 The percentage
of CD8+ lymphocytes was normal in all
patients and the CD4+:CD8+ ratio was
reversed. Because of this secondary
immunodeficiency, children with chylothorax are at risk for development
of infections. Of 7 infants with congenital chylothorax due to nonimmune
hydrops fetalis, 4 (57%) developed
nosocomial infections.162 In 2 children
who developed chylothorax after surgery for congenital heart disease, intravenous immunoglobulin G was given
prophylactically, after the development
of the chylothorax or early in the course
of septicemia.160 In a later study of 8
children with hypogammaglobulinemia
and lymphopenia attributable to chylothorax, intravenous immunoglobulin
G administration did not lead to discernible protection from infectious
complications.161
CONCLUSIONS
Chylothorax is a rare cause of pleural
effusion in children except during the
neonatal period, when it is the most
common cause. Diagnosis is made by
measurement of the triglyceride level,
determination of the pleural fluid to
serum cholesterol ratio, and demonstration of chylomicrons in the pleural
fluid. There are multiple etiologies of
chylothorax in children. Knowledge of
the anatomy and physiology of the
lymphatic system, particularly the
thoracic duct, is vital for assessment
and management. Initial treatment
involves drainage of the effusion, dietary modifications, and other medical
therapies to diminish chyle flow so that
the thoracic duct can heal. Somatostatin and octreotide are of variable
usefulness. Failure of medical management, particularly if the child
develops complications from the chylothorax, should result in early surgical
intervention. There are several surgical
procedures that have been effective in
the treatment of chylothorax. The
prognosis of children who develop
chylothorax depends on the etiology of
the effusion, its response to medical/
surgical therapies, and the complications that result from the chylothorax.
ACKNOWLEDGMENT
The author thanks Andrea B. Patters for
her editorial assistance with the preparation of this article.
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BIRTHPLACE OF BUDDHA: I enjoy ecclesiastical architecture and the architectural history of religions. While I have visited many innumerable temples,
churches, pilgrimage sites, shrines, and Buddhist temples, I have not known for
sure which one marked the birthplace of Buddha. The most commonly accepted
date for Buddha’s lifespan is 563-483 BC, but the exact date of his birth and
whereabouts of his birthplace are not known; much of what we know of his early
life comes from oral histories. As reported on CNN (World: November 25, 2013),
scientists have uncovered archaeological evidence to suggest that Buddha was
most likely born in the sixth century BC in current Nepal. Scientists excavating in
Nepal (at a site believed by many to be Buddha’s birthplace) have uncovered an
ancient Buddhist shrine dating back to that time. The Lumbini site in Nepal, in an
area bordering India and the Siwalik Range of the Himalayas, has long been
associated with Buddha, and pilgrims routinely visited the site through the 16th
century. Currently, there is a temple at the site built over earlier Buddhist temples. A sandstone pillar found here in the late 19th century has an inscription
stating that Emperor Ashoka visited this early temple in the third century BC
because it was the birthplace of Buddha. Scientists have now found evidence that
the third century temple was built over an even earlier temple. Carbon dating of
post-hole fragments date the earliest structure to the sixth century BC. Interestingly, the structure most likely was open in the middle and had a central
tree – consistent with the tradition that Buddha’s mother gave birth to him while
holding onto a tree branch. It would appear that belief, customs, and science
actually may all agree. I for one am excited about these recent archaeological
discoveries and hope to be able to visit the site soon.
Noted by WVR, MD
PEDIATRICS Volume 133, Number 4, April 2014
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