Successful Management of

Chylothorax With Etilefrine: Case

Report in 2 Pediatric Patients
Gysella Muniz, MD,​a Jennifer Hidalgo-Campos, MD,​b Maria del Carmen Valdivia-Tapia, MD,​b
Nader Shaikh, MD, MPH,​a Nilton Yhuri Carreazo, MDb,​c

Chylothorax is defined as the accumulation of chyle within the pleural abstract

space. Originally described in 1917 by Pisek, it is the most common cause
of pleural effusion in the neonatal period. The leading cause of chylothorax
is laceration of the thoracic duct during surgery, which occurs in 0.85%
to 6.6% of children undergoing cardiothoracic surgery. Few authors of
reports in the literature have looked at etilefrine, a relatively unknown
sympathomimetic, as an option for the medical treatment of chylothorax.
In this case report, we review the clinical course of 2 infants with type III
esophageal atresia who developed chylothorax after thoracic surgery and
aDivision of General Academic Pediatrics, University of
were successfully treated with intravenous etilefrine after failing initial Pittsburgh School of Medicine and Children’s Hospital
dietary and pharmacological management. of Pittsburgh of University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania; bHospital de Emergencias
Pediatricas, Lima, Perú; and cEscuela de Medicina,
Universidad Peruana de Ciencias Aplicadas, Lima, Perú
PATIENT INFORMATION oxygen desaturations. Radiography of Dr Muniz conceptualized and drafted the initial
the chest revealed obliteration of the manuscript; Drs Hidalgo-Campos, Valdivia-Tapia,
Case 1 right costodiaphragmatic angle, and and Carreazo were involved in the management
Case 1 involved a late preterm female transthoracic ultrasound revealed of both patients and conceptualized the initial
born to a 24-year-old gravida 2 para 2 a 50 mL loculated fluid collection manuscript; Dr Shaikh supervised the design and
critically reviewed the manuscript; and all authors
mother at 35 0/7 weeks of gestational that was drained after chest tube approved the final manuscript as submitted and
age (birth weight 2040 g) via normal insertion. Fluid analysis revealed agree to be accountable for all aspects of the work.
spontaneous vaginal delivery who triglycerides of 19 mg/dL, total DOI: https://​doi.​org/​10.​1542/​peds.​2016-​3309
was prenatally diagnosed with type III protein of 3 g/dL, lactate
Accepted for publication Jan 10, 2018
esophageal atresia and imperforated dehydrogenase of 356 U/L, and white
anus with associated recto-vaginal blood cell count of 360 cells per mm3 Address correspondence to Nilton Yhuri Carreazo,
MD, Avenida General Garzon 685, Jesus Maria, Lima
fistula. She underwent anoplasty and (80% polymorphonuclear cells). The 11, Peru. E-mail: yhuroc@gmail.com
fistula closure without complications chest tube was removed after 5 days
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
on day 3 of life. At 10 days of life with no detected output and resolution 1098-4275).
(DOLs), she underwent esophageal of clinical symptoms. Enteral nutrition
Copyright © 2018 by the American Academy of
repair with an end-to-end esophageal was restarted. Pediatrics
anastomosis along with closure of the
At DOL 37 the patient presented with FINANCIAL DISCLOSURE: The authors have
tracheoesophageal fistula (TEF). On
recurrent apneic episodes requiring indicated they have no financial relationships
postsurgical day 7, an esophageal-
mechanical ventilation. Transthoracic relevant to this article to disclose.
pleural fistula along with moderate
ultrasound revealed a 55 mL right FUNDING: No external funding.
stenosis of the esophageal anastomosis
pleural effusion (‍Fig 1). A chest tube POTENTIAL CONFLICT OF INTEREST: The authors
was observed.
was placed and the milky pleural fluid have indicated they have no potential conflicts of
Two weeks after TEF closure (DOL that was retrieved was characteristic interest to disclose.
25), total parenteral nutrition (TPN) of chylothorax with a triglyceride
was discontinued and enteral feeds level of 548 mg/dL, total cholesterol To cite: Muniz G, Hidalgo-Campos J, Valdivia-Tapia
with infant formula were started. level of 43 mg/dL, white blood cell MdC, et al. Successful Management of Chylothorax
With Etilefrine: Case Report in 2 Pediatric Patients.
The patient quickly developed signs count of 22 170 cells per mm3 (95%
Pediatrics. 2018;141(5):e20163309
of respiratory distress and frequent mononuclear cells), glucose level of

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220 mg/dL, and total protein level
of 4.16 g/dL. Bacterial culture of
the chylothorax did not reveal a
pathogen, and TPN was restarted.
Enteral nutrition with medium chain
triglyceride (MCT) infant formula
(Monogen) was restarted on DOL 43.
Chest tube output increased from 21
to 40 mL/kg per day to a maximum of
80 mL/kg per day on DOL 51. Enteral
feeds were stopped, and octreotide
was administered at a dose of 0.5 μg/kg
per hour increasing to a maximum
of 4 μg/kg per hour (Supplemental
Fig 2). A mild decrease in the output
was noticed, but after 3 days the
octreotide drip was discontinued
because of the prohibitive cost of
this medication. Chest tube output
at that point was 96 mL/kg per day.
On DOL 60, while the patient was
still not taking enteral feedings, the
chest tube output increased to 147
mL/kg per day, and intravenous
etilefrine infusion was started at 0.6
μg/kg per hour (‍Table 1). At the time
of initiation of therapy, the patient’s
heart rate (HR) was between 120
and 160 beats per minute (25th–75th
percentile), and the mean arterial
blood pressure (MAP) was between
46 to 52 mm Hg (5–50th percentile).
TABLE 1 Clinical Progress and Chest Tube Output in Case 1
Postoperative d
15
27
33
37
38
41
42
43
44
45
46
47
50
51
52
53
54
55
56
58
NPO, nil per os; —, not applicable.
2 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018
After increasing the rate to 1 μg/kg
per hour, HR increased to 150 to
170 beats per minute (75th–95th
percentile), and MAP was between
60 and 80 mm Hg (70th–90th
percentile). Once the infusion rate
was weaned down to 0.5 μg/kg
per hour, HR stayed between the
25th and 75th percentile and MAP
between the 75th and 90th percentile
until therapy discontinuation.
Chest tube output decreased
to 0 after 4 days of treatment,
and mechanical ventilation was
discontinued at this point. MCT
formula was started, and after 7 days
of treatment with etilefrine, TPN was
discontinued. The etilefrine drip was
discontinued at postoperative day 58.
(‍Table 1).
Case 2
Case 2 involved a term male
infant born via cesarean section
because of breech presentation
to an 18-year-old gravida 1 para
1 mother with limited prenatal
care. The infant was transferred
from an outside hospital at DOL 5
after being diagnosed with type III
esophageal atresia with associated
cardiovascular defects (atrial septal
Intake
TPN (breast milk 7 mL/kg per d)
NPO – TPN
MCTs 6 mL/kg per d
MCTs 31 mL/kg per d
MCTs discontinued NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
NPO – TPN
MCTs 64 mL/kg per d
MCTs 75 mL/kg per d
MCTs 80 mL/kg per d; TPN discontinued
MCTs 95 mL/kg per d
FIGURE 1
Chest radiograph of case 1 at postoperative
day 27. IP-NEO, inpatient-neonatology.
defect, ventricular septal defect, and
a patent ductus arteriosus). On DOL
10, an esophageal repair with an end-
to-end esophageal anastomosis was
performed along with TEF closure.
TPN was given for a total of 15 days,
and MCT formula was started at DOL
12. Two days after patent ductus
arteriosus ligation was performed
(DOL 44), milky chest tube output
was noticed (25 mL/kg per day).
Fluid analysis was compatible with
chyle (triglycerides 228 mg/dL).
Bacterial culture did not reveal a
pathogen. Intravenous etilefrine drip
was started along with MCT formula
(Supplemental Fig 2). Basal HR and
MAP were 105 to 140 beats per
Medication Chest Tube Output
— 14 mL/kg per d
— 21 mL/kg per d
— 40 mL/kg per d
— 124 mL/kg per d
— 91 mL/kg per d
Octreotide 0.5 μg/kg per h 83 mL/kg per d
Octreotide 1.5 μg/kg per h 101 mL/kg per d
Octreotide 5 μg/kg per h 85 mL/kg per d
Octreotide 4 μg/kg per h 25 mL/kg per d
Octreotide 4 μg/kg per h 20 mL/kg per d
No octreotide available 90 mL/kg per d
No octreotide available 140 mL/kg per d
Etilefrine 0.6 μg/kg per h 147 mL/kg per d
Etilefrine 1 μg/kg per h 180 mL/kg per d
Etilefrine 0.5 μg/kg per h 90 mL/kg per d
Etilefrine 0.3 μg/kg per h 0
Etilefrine 0.3 μg/kg per h 0
Etilefrine 0.2 μg/kg per h 0
Etilefrine 0.2 μg/kg per h 0
Etilefrine discontinued 0
MUNIZ et al
TABLE 2 Clinical Progress and Chest Tube Output in Case 2
Postoperative d Intake Medication Chest Tube Output
2 MCTs 90 mL/kg per d Etilefrine 0.5 μg/kg per h 25 mL/kg per d
3 MCTs 90 mL/kg per d Etilefrine 0.5 μg/kg per h 25 mL/kg per d
4 MCTs 90 mL/kg per d Etilefrine 0.5 μg/kg per h 12.5 mL/kg per d
5 MCTs 90 mL/kg per d Etilefrine 0.5 μg/kg per h 0
6 MCTs 100 mL/kg per d Etilefrine 0.5 μg/kg per h 0
7 MCTs 110 mL/kg per d Etilefrine 0.3 μg/kg per h 0
8 MCTs 110 mL/kg per d Etilefrine 0.3 μg/kg per h 0
9 MCTs 110 mL/kg per d Etilefrine discontinued 0

minute (5th–50th percentile) and 50
to 60 mm Hg (10th–50th percentile),
respectively. After therapy initiation,
HR was documented between 145
and 180 beats per minute (75th–95th
percentile), and MAP increased to
a maximum of 120 mm Hg (˃90th
percentile). Both parameters
returned to basal levels after
etilefrine was discontinued. Chest
tube output ceased after 4 days, and
etilefrine was discontinued 7 days
after treatment initiation (‍Table 2).
DISCUSSION
Chylothorax is the most common
cause of pleural effusion in
neonates.‍1 Caused by the disruption
of the thoracic duct or secondary
to increased pressure within
the superior vena cava, chyle
accumulates in the pleural space
causing different degrees of
respiratory symptoms.‍2
The general incidence of chylothorax
after cardiothoracic surgeries
is between 0.9% and 6.6%.‍3
More specifically, the repair of
congenital cardiac anomalies has
an incidence risk of 2.8%‍4 and an
incidence risk ranging from 0.2%
to 10% after esophageal surgeries.‍5
Its development is associated
with increased morbidity and
mortality, prolonged mechanical
ventilation, increased frequency in
infections, malnutrition, and venous
thrombosis.‍6
The clinician should suspect this
diagnosis on the basis of the presence
of milky or, less frequently, bloody
chest tube output after thoracic
surgery. The authors of some
data estimate the appearance of
symptoms ∼0 to 10 days between
the thoracic duct injury and the
development of chylothorax.‍7
Interestingly, the concept of thoracic
duct injury as the main cause of
postoperative chylothorax has been
recently challenged by Savla et al.‍8
These authors found, using lymphatic
imaging, that only the minority of
cases of postoperative chylothorax
were the result of injury to the
thoracic duct.
The diagnosis is confirmed by
observation of the presence of
chylomicrons or triglyceride levels
being ˃110 mg/dL.‍4 Both of our
patients had levels well above this
cutoff value. Another characteristic is
the presence of leukocyte cell count
being ˃1000, with more than 90%
lymphocytic predominance. As a
diagnostic intervention, a trial of fatty
foods by mouth or via nasogastric
tube can be done to observe a
dramatic change in color, as well as
the presence of triglycerides and
chylomicrons in the pleural fluid.‍9
Given the lack of resources, diagnosis
was based on clinical data (analysis
of the pleural fluid analysis and chest
radiography). No other diagnostic
tests (eg, dynamic contrast-
enhanced magnetic resonance
lymphangiography and intranodal
lymphangiography) were used.
The treatment of this condition
requires dietary modifications and
therapeutic agents like octreotide
and etilefrine that can decrease chyle
production.‍9,​10
‍ Surgical treatment
and, more specifically, the ligation
of the thoracic duct is also available
in case of medical treatment failure,
although this is usually considered
as a secondary option and is usually
associated with a high failure rate.‍11
Dietary modifications, such as the
use of a fat-free diet along with
MCTs, which are directly absorbed
through the venous portal system
bypassing the lymphatics, help
decrease chyle production. The use of
TPN, if available, is another efficient
therapeutic intervention that will
help decrease chyle production and
leakage.‍5,​12
‍ In the first case described,
the patient was first started on TPN
and then transitioned to Monogen, a
low-fat infant formula that contains
80% MCTs. The second patient was
immediately started on MCT formula
along with etilefrine drip.
Octreotide is a widely used and
effective medication in the treatment
of chylothorax. With a 2- to 6-hour
half-life, this synthetic somatostatin
analog decreases chyle production
by inhibiting gastric, pancreatic,
and intestinal secretions.‍11 Some
of its secondary effects reported
in children include hyperglycemia,
hypothyroidism, nausea, diarrhea,
necrotizing enterocolitis, and liver
dysfunction.‍13 Given the cost of
octreotide, the use of it might be
prohibitive in many countries
worldwide. This imposes the need of
establishing other affordable and safe
options in the treatment of pediatric
patients.
Although there is no Food and Drug
Administration–approved indication
of this medication, etilefrine is
commonly used in the treatment

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of postural hypotension, syncope,
and sickle cell priapism. With this
sympathomimetic, both α and β
adrenergic receptors are
stimulated, arterial and venous
tone are improved, and myocardial
activity is enhanced.‍14 Smooth
muscle contraction within the
thoracic duct causes a decrease
in chyle flow, therefore decreasing
or stopping the effusion into
the pleural space.‍10,​15
‍ Potential
side effects include palpitations,
ventricular arrhythmias, chest pain,
angina pectoris, and hypertension,
which have been described in
adults taking etilefrine by mouth.
If intravenous infusion is too
rapid, tachycardia, tremor, and
piloerection may occur.‍14
To the best of our knowledge,
there are no reports of etilefrine
use in the treatment of children
and/or neonates with chylothorax.
Of the <8 articles published in the
literature in which authors describe
etilefrine as a therapeutic option,
only a few of the authors discuss in
more detail its use and only report
outcomes in adult patients. Ohkura
et al‍16 presented a case report of
2 patients who developed post
esophagectomy chylothorax and
were successfully managed with a
combination of octreotide, etilefrine,
and pleurodesis. Guillem et al‍15,​17
‍ 1. van Straaten HL, Gerards LJ, Krediet
published both a case report of
3 patients and a case series of 10
patients with thoracic or abdominal
chyle leaks after thoracic surgical
procedures. In this last case series,
a total of 11 etilefrine intravenous
infusions were given (patient 10
required a second infusion cycle
after reoperation). One patient
with postoperative heart failure
required infusion withdrawal
because of an interaction with
other sympathomimetic drugs
(dopamine and dobutamine),
and another patient required
reduced doses, without stopping
the infusion, because of an increased
HR and blood pressure.
4 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018
The use of etilefrine could be a novel
option in the conservative treatment
of postoperative chylothorax in
pediatric patients, but given the
lack of data, more prospective trials
are needed to establish its cost-
effectiveness, efficacy, and safety in
the pediatric population.
In our 2 patients, etilefrine
caused a significant reduction
in chyle output 3 days after
starting treatment, and complete
resolution was observed after
4 days of treatment with no
significant side effects.
ACKNOWLEDGMENT
We thank Dr Judy Martin for her
valuable suggestions and review
of the article.
ABBREVIATIONS
DOL: day of life
HR: heart rate
MAP: mean arterial blood
pressure
MCT: medium chain triglyceride
TEF: tracheoesophageal fistula
TPN: total parenteral nutrition
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 Successful Management of Chylothorax With Etilefrine: Case Report in 2
Pediatric Patients
Gysella Muniz, Jennifer Hidalgo-Campos, Maria del Carmen Valdivia-Tapia, Nader
Shaikh and Nilton Yhuri Carreazo
Pediatrics originally published online April 27, 2018;

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN:
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 Successful Management of Chylothorax With Etilefrine: Case Report in 2
Pediatric Patients
Gysella Muniz, Jennifer Hidalgo-Campos, Maria del Carmen Valdivia-Tapia, Nader
Shaikh and Nilton Yhuri Carreazo
Pediatrics originally published online April 27, 2018;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/early/2018/04/25/peds.2016-3309

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN:
.

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