Index of Suspicion in the Nursery

Megan Wills Kullnat, Steven N. Weindling, Robert A. Darnall, S. Hossein Fakhraee,

M. Kazemian and Sh. Noripour
NeoReviews 2008;9;e124-e128
DOI: 10.1542/neo.9-3-e124

The online version of this article, along with updated information and services, is
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index of suspicion in the nursery

Case 1 Presentation

The reader is encouraged to write

possible diagnoses for each case
before turning to the discussion.
We invite readers to contribute
case presentations and discussions.
Please inquire first by contacting
Dr. Philip at aphilip@stanford.edu.

Author Disclosure
Drs Wills Kullnat, Weindling, Darnall,
Fakhraee, Kazemian, and Noripour
did not disclose any financial

A 4-day-old term male infant develops progressive irritability with pallor

and poor capillary refill. He has been
hospitalized in the intensive care
nursery for refractory hypoglycemia
since birth. He has no risk factors for
hypoglycemia, and his glucose concentrations have stabilized to normal
limits with the administration of intravenous 20% glucose through an
umbilical venous catheter (UVC).
Imaging of the UVC initially showed
placement in the liver; the UVC was
withdrawn 1 to 15 cm and confirmed
by chest radiograph to be in the right
atrium.
The infant has been otherwise
well, with stable vital signs and unremarkable laboratory values except for
glucose. At the onset of irritability,
glucose concentrations are normal.
He is afebrile, but develops rapidly
progressive hypoxia and bradycardia
that requires the administration of
100% oxygen. Transillumination of

the chest wall does not suggest pneumothorax. A chest radiograph reveals
a cardiac silhouette at the upper limit
of normal, but well-aerated lung
zones without infiltrates (Fig. 1).
A complete blood count (CBC) and
blood cultures are obtained, and prophylactic ampicillin and gentamicin
are initiated. Electrocardiography reveals normal results. Four extremity
blood pressures are attempted but
are unable to be recorded. The infant
deteriorates to asystole, is intubated
with an endotracheal tube, and receives cardiopulmonary resuscitation
(CPR).
During resuscitation, epinephrine
is administered via the endotracheal
tube, and bicarbonate and fluid repletion are provided. A prostaglandin drip is started. When these interventions do not result in clinical
improvement, intravenous epinephrine is administered without response. Within 10 minutes of resuscitation, beside echocardiography is

relationships relevant to these cases.

Figure 1. Chest radiograph showing the cardiac silhouette at the upper limit of
normal, but no lung infiltrates.
e124 NeoReviews Vol.9 No.3 March 2008

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index of suspicion in the nursery

Figure 2. Echocardiographic image.

obtained and reveals the diagnosis

(Fig. 2).

Case 2 Presentation
A 10-day-old male infant is admitted
to the hospital because of abdominal distention. He was delivered at
term by repeat cesarean section following an uncomplicated pregnancy.

His mother is a 30-year-old G2P2

woman whose blood group is O
and whose serology for hepatitis B is negative. Apgar scores were
8 and 9 at 1 and 5 minutes, respectively. His birthweight was 3,800 g.
Physical examination at birth revealed
swelling of the face and extremities as
well as abdominal distention. The facial and extremity swelling subsided

gradually, but the abdominal distention has persisted.

The baby is the second child in
the family; the first child is a 2-yearold healthy male. There is no consanguinity between the parents. At
the time of admission, the patients
weight is 3,950 g, length is 52 cm,
head circumference is 37 cm, and
abdominal girth is 39 cm. The baby
appears afebrile, active, and in no
distress. Physical examination reveals abdominal distention, diastasis recti, and moderate hydrocele.
Shifting dullness and a fluid wave
are evident on abdominal percussion.
Results of laboratory evaluation, including complete blood count, serum
electrolytes, blood urea nitrogen, serum creatinine, liver function tests,
TORCH serology, thyroid function
tests, direct Coombs test, serum bilirubin, total protein, cholesterol, triglyceride, urinalysis, and maternal
studies for autoimmune diseases, are
unrevealing. Chest radiography, echocardiography, and electrocardiography
findings are normal. Abdominal ultrasonography shows a moderate amount
of peritoneal fluid. Contrast radiography of the gastrointestinal tract appears
normal. A procedure is performed that
leads to the diagnosis.

NeoReviews Vol.9 No.3 March 2008 e125

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index of suspicion in the nursery

Case 1 Discussion
The differential diagnosis for a neonate who has bradycardia and hypoxia progressing to asystole can be
divided broadly into cardiac, pulmonary, and infectious causes. Other
causes exist but are not included in
this discussion. For this baby, pulmonary causes, including tension
pneumothorax and pneumonia, were
ruled out by chest radiography. Results of the CBC and blood cultures
were not immediately available but
ultimately were normal. Given the
gravity of the infants condition,
the clinicians decided to initiate prophylactic antibiotic therapy. Congenital heart disease was high on the
list of differential diagnoses, given
the infants hypoxia, rapid decompensation, and failure to respond to
resuscitative measures. This concern
prompted bedside echocardiography, which revealed a large circumferential pericardial effusion (PCE).
There were no spontaneous cardiac
contractions in the absence of chest
compressions. Emergent pericardiocentesis was performed in conjunction with CPR, and 15 mL of clear
fluid was withdrawn from the pericardial space. After removal of the
fluid, the infants heart resumed
spontaneous electrical and mechanical activity.
Echocardiography
additionally
demonstrated the path of the UVC
across the foramen ovale into the left
atrium. The catheter was retracted
into the vena cava. The pericardial
fluid was sent for laboratory analysis
and was found to contain a glucose
content of more than 1,000 mg/dL
(55.5 mmol/L). No other congenital defects were evident on imaging.

The Condition
PCE and cardiac tamponade are
rarely reported complications of central venous catheter (CVC) use in the
neonatal population; the true incie126 NeoReviews Vol.9 No.3 March 2008

dence is unknown. One study suggests that PCE occurs in 1% to 3% of

infants who have a CVC. (1) A recent
review of 61 cases in the literature
indicates that the median gestational
age at birth of affected infants is
30.0 weeks and birthweight is 1.0 kg.
(2) Studies have examined various
routes of CVC access but have not
found a specific route associated with
increased risk of extravasation or with
a higher mortality rate. Moreover, it
does not appear that certain types of
catheters predispose to such complications.
The median number of days from
catheter insertion to the development of symptoms of PCE is
3.0 days. This is similar to the current
case, which presented on the fourth
day of receiving intravenous dextrose. This timeline suggests that this
infants cardiac compromise more
likely was caused by migration of the
catheter from the right atrium than
by initial placement of the CVC. Furthermore, initial placement was confirmed by chest radiograph. Proposed causes of PCE in the literature
include lodging of the CVC tip
against the contracting heart or damage to the endocardium, either by
direct puncture or by hyperosmolar
infiltrates. The latter has been supported by autopsy reports demonstrating transmural necrosis, myosclerosis, or thrombus formation. (1)
With increasing long-term CVC
use in intensive care units, reports
of PCE and cardiac tamponade in
association with infusion of parenteral nutrition are becoming more
frequent. The neonatal pericardial
membrane is fragile and more susceptible to damage and infiltration
by foreign instrumentation than is the
adult counterpart. Small amounts of
infused fluid can alter cardiac contractility dramatically within a short
period of time. Moreover, portions
of the developing neonatal heart lack

myocardium, and the thin endocardial/

epicardial layer is particularly vulnerable to perforation.
Autopsy or surgical findings have
demonstrated myocardial necrosis,
thrombosis, or perforation in the following sites in descending order of
incidence: right atrium, left atrium,
right ventricle, superior vena cava,
right atrial junction, and left subclavian vein.

Diagnosis
The diagnosis of PCE can be confirmed by echocardiography or pericardiocentesis. Clinical suspicions for
PCE should prompt further evaluation by echocardiography. Some 61%
of cases of PCE present with rapidly
progressive cardiorespiratory decompensation resulting from cardiac
tamponade; 36% present with unexplained cardiorespiratory instability.
(2) Milder cases of effusion presenting with bradycardia alone have been
reported. In these cases, withdrawal
of the catheter led to symptomatic
improvement and resolution of the
effusion without intervention. Infants have presented less frequently
with a new murmur, distant heart
sounds, distended neck veins, metabolic acidosis, narrowed pulse pressure, or pulsus paradoxus. (1) Seven
percent of infants had pleural effusions associated with PCE. (2) It
should be noted that complications
related to CVC displacement are not
isolated to the heart; cases have been
reported in the literature of intrathoracic, intra-abdominal, or retroperitoneal extravasation from CVC use,
which present more insidiously than
in infants who have cardiac involvement.
A qualitative increase in cardiac
silhouette on chest radiograph has
been noted in 41% of cases and an
increased cardiothoracic ratio in
17%. Such a change in cardiothoracic
ratio may be suggestive of the diag-

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index of suspicion in the nursery

nosis but is insensitive. In the present

case, the heart border appeared to be
within the upper limits of normal but
was noted retrospectively to be
smaller in subsequent films following
treatment.
The general consensus in the literature favors routine radiographic
determination of CVC location following placement. The CVC tip
should be located within the vena
cava approximately 1 cm outside of
the cardiac silhouette in preterm infants and 2 cm outside the silhouette
in term infants. This typically correlates with the 8th to 9th thoracic
vertebral body on chest radiograph,
although ranges as variable as the 6th
to 11th vertebral bodies have been
reported. (3) Certainly, this level of
determination can be difficult or
even impossible to ascertain, although accuracy can be increased by
using a radio-opaque catheter or
marker on the tip of the catheter to
facilitate monitoring. Once initial
placement has been confirmed, films
may be repeated every few days to
evaluate for line migration. Finally,
avoidance of excessive manipulation
and mobilization of infants may reduce the risk of line displacement.
The causative agent can be confirmed with biochemical testing of
the pericardial fluid. In 97% of cases,
the pericardial fluid composition is
identical to the infused fluid.

associated with heightened awareness and clinician education. (2)

Mortality is much lower in infants
treated with pericardiocentesis at 8%
compared with neonates who do not
receive an intervention (75%). Gestational age at birth, birthweight, days
after birth at PCE diagnosis, and days
until PCE diagnosis do not appear to
affect the prognosis.
Long-term follow-up of affected
neonates is limited. To date, none of
the known cases of PCE have developed subsequent cardiac sequelae,
including constrictive pericarditis.

Treatment
Once the diagnosis has been made,
the PCE should be drained emergently in any infant who has a CVC,
cardiorespiratory compromise, and
high clinical suspicion for PCE. Case
studies have reported attempts to aspirate the extravasating CVC fluid
directly without success; the failure
rate has been attributed to thrombus
formation at the tip of the CVC.
Aspiration can be attempted, but
should not delay pericardiocentesis.
Fluid infusion through the line
should be discontinued and the central line retracted. Complete removal
of the catheter may not be necessary;
the literature reports continued successful use of the CVC following retraction.

Lessons for the Clinician

Prognosis
Death from PCE has been estimated
to occur in 30% to 67% of cases and
depends on the rapidity of decompensation and the absence/presence
of warning signs. (2)(4) Early and
aggressive intervention clearly affects
survival rates. In a comprehensive review of CVC-related PCE and tamponade at the authors institutions as
well as in the literature, the 0% mortality in the authors institutions was

Given the severity, morbidity, and

potential mortality of PCE and cardiac tamponade, it is crucial for the
clinician to consider the diagnosis
when evaluating a neonate who develops sudden cardiorespiratory decompensation. Clinical suspicion
should be particularly high for any
neonate who has such symptoms and
a CVC. Although historically rare, an
increasing number of cases in the literature suggest that the risk of this
complication is rising and may con-

tinue to do so while CVC use and

parenteral nutrition remain the
mainstay of treatment in neonatal
populations. (Megan Wills Kullnat,
MD, Steven N. Weindling, MD, Pediatric Cardiology, Robert A. Darnall,
MD, Neonatology, Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Dartmouth, NH)

References
1. Traen M, Schepens E, Laroche A, et al.
Cardiac tamponade and pericardial effusion
due to venous umbilical catheterization.
Acta Paediatr. 2005;94:626 633
2. Nowlen TT, Rosenthal GL, Johnson
GL, et al. Pericardial effusion and tamponade in infants with central catheters. Pediatrics. 2002;110:137142
3. Green C, Yohannan MD. Umbilical arterial and venous catheters: placement, use
and complications. Neonatal Netw. 1998;
17:2328
4. Sehgla A, Cook V, Dunn M. Pericardial
effusion associated with an appropriately
placed umbilical venous catheter. J Perinatol. 2007;317319

Case 2 Discussion
Needle aspiration of the ascitic fluid
revealed a milky fluid that had the
following characteristics:

White blood cell count: 3.5

103/mcL (3.5 109/L) with 5%
neutrophils and 95% lymphocytes
Red blood cell count: 5.0 103/
mcL (5.0 109/L)
Protein: 3.1 mg/dL (31 g/L)
Glucose: 175 mg/dL (9.7 mmol/L)
pH: 7
Specific gravity: 1.015
Cholesterol: 115 mg/dL (3.0
mmol/L)
Triglycerides:
1,354
mg/dL
(15.3 mmol/L)
Amylase: 17 mg/dL
Lipase: 13 mg/dL
Gram stain and culture: negative

Chylous ascites was diagnosed on the

basis of the high triglycerides content
of the ascitic fluid.
NeoReviews Vol.9 No.3 March 2008 e127

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index of suspicion in the nursery

The infants diet was changed to

a high-protein, low-fat formula that
contained medium-chain triglycerides (MCTs) as well as human milk
and discharged in good condition.
On weekly follow-up in the outpatient clinic, the abdominal distention
is improving clinically, and serial abdominal ultrasonographic studies
document lessening of the ascitic
fluid. No further medical or surgical
intervention has been needed.

Diagnosis and Differential

Diagnosis
Generalized abdominal distention in
the newborn could be due to various conditions, including gastrointestinal obstruction, visceromegaly,
tumors, peritonitis, or ascites. Such
imaging studies as radiography, contrast studies, ultrasonography, and
computed tomography scan or magnetic resonance imaging could be
helpful in evaluating abdominal distention.
If there is any question of the presence of the ascites, abdominal paracentesis and analysis of the ascitic
fluid is the gold standard diagnostic
procedure. Ascitic fluid in the newborn may be of chylous, urinary, bilious, or pancreatic origin. It also
could be due to generalized edema
caused by hydrops fetalis, congestive
heart failure, or congenital nephrotic
syndrome. Chylous ascites is the
most common form of congenital ascites and is seen more frequently in
males. This condition is due to the
lack of sufficient connections between lymphatic channels. Occasionally, chylous ascites in the newborn

e128 NeoReviews Vol.9 No.3 March 2008

may be due to trauma to the thoracic

duct, which can cause leakage of the
lymph into pleural or peritoneal cavities. If abdominal paracentesis is performed before enteral feeding is
started, a clear fluid will be obtained.
After enteral feeding, the fluid becomes milky and has a high triglycerides content. Chylous ascites is diagnosed when the concentration of
triglycerides in the fluid is more than
200 mg/dL (2.3 mmol/L). The leukocyte count may be high, with a
predominance of lymphocytes, and
the protein content varies between
2.5 and 7 g/dL (25 and 70 g/L).

Management
If a primary pathology is causing chylous ascites, it should be treated. If a
primary cause cannot be found (the
case for most neonates who have
congenital ascites), the first therapeutic option is feeding of a highprotein, low-fat milk formula that
contains MCTs. MCTs are absorbed
directly into the intestinal epithelial
cells and transported as free fatty acids and glycerol directly to the liver
via the portal vein. Thus, the production and flow of lymph are diminished. If the patient does not respond
to this conservative management,
bowel rest and parenteral nutrition
should be tried. In some cases, octreotide, a somatostatin analog, has
been used with some success. Surgical intervention such as peritoneovenous shunt or lymphatic microsurgery may be required if
conservative and medical therapies
fail.

Lessons for the Clinician

Pathologic abdominal distention in a
newborn calls for appropriate imaging studies. If ascitic fluid is suspected clinically and confirmed by
imaging studies, needle aspiration
and analysis of the peritoneal fluid
should be performed for final diagnosis. Milky ascitic fluid whose triglycerides content is more than
200 mg/dL (2.3 mmol/L) confirms
the diagnosis of chylous ascites,
which is the most common form of
congenital ascites. The management
of this condition usually is conservative. (S. Hossein Fakhraee, MD,
FAAP, M. Kazemian, MD, Sh. Noripour, MD, Division of Neonatology,
Mofid Childrens Hospital, Tehran,
Iran)

Suggested Reading
Andreou A, Papouli M, Papavasiliou V, Badouraki M. Postoperative chylous ascites
in a neonate treated successfully with
octreotide: bile sludge and cholestasis.
Am J Perinatol. 2005;22:401 404
Camoglio FS, Dipaola G, Cervellione RM,
et al. Treatment of neonatal chylous ascites using a modified Denver peritoneovenous shunt: a case report. Pediatr
Med Chir. 2003;25:145147
Lee YY, Soong WJ, Lee YS, Hwang B. Total
parenteral nutrition as a primary therapeutic modality for congenital chylous
ascites: report of one case. Acta Paediatr
Taiwan. 2002;43:214 216
Liang X, Liu X, Lu X, Yang M. The causes of
chylous ascites: a report of 22 cases
Zhonghua Nei Ke Za Zhi. 1999;38:
530 532
Machmouchi M, Amin A, Lanjaoui I, Jacobs A, Hatoum C, Al Zahrani D. Congenital chylous ascites: report of four
cases and review of the literature. Ann
Saudi Med. 2000;20:436 439

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Index of Suspicion in the Nursery

Megan Wills Kullnat, Steven N. Weindling, Robert A. Darnall, S. Hossein Fakhraee,
M. Kazemian and Sh. Noripour
NeoReviews 2008;9;e124-e128
DOI: 10.1542/neo.9-3-e124

Updated Information
& Services

including high-resolution figures, can be found at:

http://neoreviews.aappublications.org/cgi/content/full/neoreview
s;9/3/e124

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