Documente Academic
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NOVEMBER 2014
Vol. 35 No. 11
www.pedsinreview.org
Kaslovsky, Sadof
Respiratory Failure
Vo, Kharasch
REAL-LIFE CASES CUTTING-EDGE CLINICAL REVIEWS BEST PRACTICES FOR PATIENT CARE
ONLINE
Visual Diagnosis:
6-Month-Old Boy With
Leg Pain
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aeruginosa, and other gram-negative organisms. Antibiotic treatment should again be directed at the most common pathogens
for 7 to 10 days, taking into account the possibility of
multidrug-resistant organisms. If feasible, serial surveillance
of endotracheal aspirate specimens can identify multidrugresistant pathogens and help tailor antibiotic therapy.
The risk of VAT peaks at approximately 4 days after intubation, with an estimated incidence of 2% to 11%. The onset of
bacterial tracheitis in children with long-standing tracheotomies
is less predictable, with a reported incidence of less than 1%.
In general, tracheotomy-associated tracheitis is not aggressive
and, if there is close follow-up, can be treated in the outpatient setting with oral antibiotics, topical ciprooxacin and
dexamethasone, or tobramycin and dexamethasone drops
directed into the tracheotomy for several days. Recurrence
of tracheitis is more common in children with a long-term
tracheotomy.
During the past several decades, the incidence, diagnosis, and management of bacterial tracheitis have been
inuenced by new vaccines and by the heightened awareness among physicians of the alarmingly high morbidity
associated with delayed recognition. Despite its low incidence, clinicians must consider the possibility of bacterial
tracheitis in any patient with acute respiratory decompensation
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Vol. 35 No. 11
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contents
Pediatrics in Review
ARTICLES
456
465
476
Respiratory Failure
487
493
496
497
Correction
Bacterial Tracheitis
Connie Y. Kuo, Sanjay R. Parikh
ONLINE
e53
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Educational Gap
Hearing loss is a common condition presenting in children. Speech and
language outcomes for children with hearing loss are related to
identication of the hearing loss and to the degree of hearing loss. Early
identication and appropriate, prompt intervention yield better
outcomes. An understanding of the relevant anatomy, common causes,
testing strategies, and management of hearing loss can help the primary
care physicians maximize communication development in children.
Objectives
Hearing loss is a common condition in children, with 1 in 1000 live births affected
with severe to profound permanent hearing loss. The prevalence increases to 6 in
1000 when all degrees of hearing loss, mild to profound, are considered. As
children age, the prevalence increases, and by age 18 years, 17 in 1000 individuals
are affected by some degree of permanent hearing loss. This makes hearing loss
more prevalent that diabetes mellitus and all pediatric cancers. (1) These
numbers, however, do not take into account all the children who are affected
by long-standing chronic effusions, which, though temporary, can have a signicant effect on speech and language development if not identied and
appropriately treated.
Hearing loss in children can derive from many forms. It can be congenital
(present at birth), genetic, syndromic, nonsyndromic, acquired, and/or progressive. It may manifest as conductive, sensorineural, or mixed hearing loss. The
evaluation, diagnosis, and management of children with hearing loss will involve
a multidisciplinary effort by pediatricians, otolaryngologists, audiologists, deaf
educators, speech and language pathologists, early intervention specialists, and
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Pediatrics in Review
Vol. 35 No. 11
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458
Pediatrics in Review
TABLE 1.
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Pediatrics in Review
TABLE 2.
CAUSE
DESCRIPTION
Autosomal dominant
Waardenburg syndrome
Stickler syndrome
Progressive SNHL
Cleft palate present and spondyloepiphyseal dysplasia also may be present
Often have severe myopia which increases risk for retinal detachment
Branchiootorenal syndrome
Neurobromatosis types 2
Autosomal recessive
Usher syndrome
Pendred syndrome
X-linked
Alport syndrome
Abbreviations: CHLconductive hearing loss; CTcomputed tomography; ECGelectrocardiography; MRImagnetic resonance imaging; SNHLsensorineural
hearing loss.
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Pediatrics in Review
Summary
On the basis of strong research, universal newborn screening
should be performed before age 1 month with repeat or followup testing for those who do not pass performed before age 3
months and intervention started before age 6 months.
On the basis of strong research and consensus statement,
tympanostomy tubes should be considered for individuals with
bilateral persistent middle ear effusion for 3 months or greater
and a documented conductive hearing loss.
On the basis of consensus statement, all children with suspected
hearing loss should have an age appropriate hearing test.
On the basis of strong research, the most common form of
congenital hearing loss is genetic. Most of this is nonsyndromic
hearing loss.
References
1. Morton NE. Genetic epidemiology of hearing impairment. Ann N Y
Acad Sci. 1991;630:1631
2. American Academy of Pediatrics, Joint Committee on Infant
Hearing. Year 2007 position statement: principles and guidelines
for early hearing detection and intervention programs. Pediatrics.
2007;120(4):898921
3. Harrison M, Roush J, Wallace J. Trends in age of identication and
intervention in infants with hearing loss. Ear Hear. 2003;24
(1):8995
13. Tomblin JB, Oleson JJ, Ambrose SE, Walker E, Moeller MP. The
inuence of hearing aids on the speech and language development
of children with hearing loss. JAMA Otolaryngol Head Neck Surg.
2014;140(5):403409
Vol. 35 No. 11
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463
PIR Quiz
1. The goal of the universal newborn hearing screening (UNHS) program is which of the
following:
A. Identify all children with moderate hearing loss by age 2 months and initiate
intervention by age 4 months.
B. Identify all children with permanent hearing loss by age 3 months and initiate
intervention by age 4 months.
C. Identify all children with moderate hearing loss by age 1 month and initiate
intervention by age 4 months.
D. Identify all children with permanent hearing loss by age 3 months and initiate
intervention by age 6 months.
E. Identify all children by age 1 month and initiate intervention by age 3 months.
2. A 3-year-old girl presents to your clinic with a 2-month history of otitis media, resistant to
amoxicillin and amoxicillin clavulanate. On otoscopic examination, she has
nonerythematous tympanic membranes, which are dull and do not move on insufation.
You perform a tympanogram in your ofce. Which of the following tympanograms would
be most consistent with an ear effusion?
A.
B.
C.
D.
E.
Type
Type
Type
Type
Type
A.
B.
C.
D.
E.
3. An infant with auditory neuropathy spectrum disorder presents to your clinic. You know
this disorder involves a defect in the signal transmission of sound from the inner ear to the
brain. Which of the following hearing screen results would you expect in this patient?
A.
B.
C.
D.
E.
10%.
25%.
50%.
75%.
100%.
5. A 7-year-old boy is admitted to the hospital with fever and rash and is treated for bacterial
meningitis. He passes a hearing screen in the hospital before discharge. As you prepare his
discharge consultations, you schedule him for follow-up audiology testing. Which of the
following schedule is most appropriate?
A.
B.
C.
D.
E.
464
Pediatrics in Review
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2014 Pediatrics in Review
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Practice Gap
The 2007 National Heart, Lung and Blood Institute expert panel asthma
guidelines recommend that spirometry be part of routine asthma
diagnosis and monitoring of therapy, yet only 35% of pediatric practices
use spirometry for patients with asthma. Pediatricians should be aware
that routine ofce spirometry is feasible, practical, and important for
optimizing care for children with respiratory symptoms or risk of lung
disease.
Objectives
INTRODUCTION
Who?
Most children older than 5 years, who can cooperatively take deep breaths, can be
coached to perform a good spirometry test. Younger children or those with
developmental delays, certain disabling conditions, or poor behavior may not be
willing or able to perform the test. (For those too young to voluntarily exhale into
Vol. 35 No. 11
NOVEMBER 2014
465
the spirometer, impulse oscillometry is an alternate technique that requires nothing more than passively breathing
into a mouthpiece. Description of this tool is beyond the
scope of discussion for this paper.) (2) Any child with
respiratory symptoms or who is at risk for lung disease
should have spirometry performed routinely. The 2007
NHLBI expert panel asthma guidelines recommend that
spirometry be performed at diagnosis, rather than relying
on measures of peak expiratory ow rates. (3)
What?
Spirometers can be of 2 general types: volume displacement
or ow measurement. Those that measure volume have
a (usually 10-L) drum with a piston, such that the change in
volume over time is measured directly, and ow rates are
calculated (change of volume over time). These devices are
computer linked and usually not easily portable, tend to be
more costly, and most likely would not be useful to a primary
care practice.
Flow-sensing devices can be handheld and are easily
portable from room to room in the ofce. They use disposable sensors, referred to as pneumotachometers, which
sense the ow over time. This measurement of ow is used
to calculate the volumes. These devices may be selfcontained or connected to a laptop or desktop computer.
Any spirometer used in an ofce setting should meet the
American Thoracic Society/European Respiratory Society
recommendations for spirometry (available online at http://
www.thoracic.org/statements/resources/pft/pft2.pdf). (4)(5)
The rst chapter of this document is essential reading for
all clinical staff, with descriptions of standards for hygiene,
calibration, quality control, and other maintenance issues. (5)
Measurements made by the spirometer are as follows:
Forced vital capacity (FVC): the total volume of air exhaled
after maximal inhalation.
Forced expiratory volume in 1 second (FEV1): the volume
of air exhaled in the rst second. Reversibility after
inhaled bronchodilator is determined by an increase in
FEV1 of 12% or more or 200 mL from baseline.
Ratio of FEV1 to FVC.
Peak expiratory ow rate: the highest ow obtained
during the forced expiratory maneuver, expressed as liters
per second. This is different than the peak ow meter
readings, which are expressed in liters per minute.
Forced expiratory volume between 25% and 75% of vital
capacity (FEF25%-75%): the ow in the midportion of the
forced expiratory maneuver, which is a reection of the
ow from the smaller airways.
Forced expiratory time: the time that the patient sustains
the expiratory maneuver.
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Pediatrics in Review
Why?
There are many reasons to perform spirometry in a pediatric
patient:
To establish whether pulmonary mechanics are normal in
a child with symptoms.
To dene the nature and severity of any pulmonary
dysfunction (obstructive vs restrictive defect).
To dene the site of airway obstructioncentral vs
peripheral or intrathoracic vs extrathoracic.
To follow the course of pulmonary disease or assess the
effect of therapy.
To establish the presence or absence of airway reactivity.
To assess the risks of diagnostic or therapeutic procedures.
To monitor for adverse effects of chemotherapy or radiation therapy.
To predict prognosis or assess disability and to assess the
effect of disease on lung growth.
You can do this in your ofce! It is important to identify
what barriers exist in your ofce to map out a plan for
sustainable change. Time, patient ow, and quality are often
cited as barriers to spirometry implementation. It is important to remember that each practice is different. Some
practices will group asthma visits that include spirometry
(each practitioner has several dedicated asthma sessions
a month); others will prereview patients before each session
to develop a better patient ow strategy to allow for spirometry. An individualized implementation that matches existing
practice culture appears to be the best strategy to successfully
change and sustain practice patterns. (6)
Although regional (7) and distance or Internet-based
training efforts (8) have been successful at improving the
spirometry capacity and guideline-based asthma care in
primary care pediatricians ofces, many busy practitioners
still struggle with implementing and sustaining routine
spirometry into their busy practice.
The planned asthma visit (Table 1) is a tool that can be
used to implement spirometry in the busy practice. (9) In
this model, patients with asthma can be proactively assessed
for control with an asthma control test and spirometry. This
is a time when trained ofce staff can help to identify asthma
triggers in the home, school, and work environment. Medications and administration technique can be reviewed with
the patient and family, and immunizations, such as inuenza, can be given. Spirometry can also be performed with
a bronchodilator for initial visits to help establish reversibility. Spirometry without a bronchodilator can be performed at follow-up visits to monitor control. All this can
be completed before the practitioner enters the room. The
practitioner will review all the results, examine the patient,
and create or update a written action plan. Follow-up can be
COMMON PITFALLS
Calibration is a common pitfall. Because atmospheric pressure and temperature are continuously changing, volumedisplacement spirometers may have to be calibrated daily.
This requires a xed-volume (usually 3-L) syringe with
which to pump air into and out of the spirometer. The
device then recognizes this exact volume as 3 L and is then
TABLE 1.
All patients >4 years old receive the Asthma Control Test
Spirometry is performed with bronchodilator at the initial visit to
establish diagnosis (or without bronchodilator for follow-up)
Practitioner reviews results
Asthma action plan is reviewed or created
Follow-up appointment 16 months based on severity and/or
control
Ofce visit code 99214
Simple spirometry code 94010
Spirometry with bronchodilator code 94060
NORMAL SPIROMETRY
In general, parameters above 80% of predicted (and an
FEV1/FVC ratio >80%) are considered normal results
(Figure 1). (19)
FLOW-VOLUME LOOPS
A plot of ow vs volume is generated during spirometry and
should be examined to determine the acceptability of the test
and to give a preliminary idea of the interpretative pattern. A
normal ow-volume loop will show the vital capacity on the
Vol. 35 No. 11
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Pediatrics in Review
BRONCHODILATOR RESPONSE
In general, an increase in FEV1 of greater than 12% (for low
lung volumes, minimum change of 200 mL) and/or an
increase in FEF25%75% of greater than 20% is considered
a signicant positive response to a bronchodilator (Figure 3).
(19)
EVIDENCE-BASED SUMMARY
On the basis of some research and consensus,_the 2007
NHLBI expert panel asthma guidelines recommend
Vol. 35 No. 11
NOVEMBER 2014
469
spirometry be part of routine asthma diagnosis and monitoring of therapy. (3) Just as hypertension is managed by
measuring blood pressure regularly and diabetes is managed by checking blood glucose levels, so should lung
References
1. Dombkowski KJ, Hassan F, Wasilevich EA, Clark SJ. Spirometry use
among pediatric primary care physicians. Pediatrics. 2010;126
(4):682687
2. Galant SP, Nickerson B. Lung function measurement in the
assessment of childhood asthma: recent important developments.
Curr Opin Allergy Clin Immunol. 2010;10(2):149154
3. National Asthma Education and Prevention Program. Expert Panel
Report 3: Guidelines for the Diagnosis and Management of Asthma;
National Heart, Blood, and Lung Institute. 2007. http://www.nhlbi.nih.
gov/guidelines/asthma/asthgdln.htm. Accessed September 25, 2014
4. Miller MR, Hankinson J, Brusasco V, et al. ATS/ERS Task Force.
Standardization of spirometry. Eur Respir J. 2005;26(2):319338
5. Miller MR, Crapo R, Hankinson J, et al. General considerations for
lung function testing. Eur Respir J. 2005;26:153161.
6. Ragazzi H, Keller A, Ehrensberger R, Irani AM. Evaluation of a practice-based intervention to improve the
management of pediatric asthma. J Urban Health. 2011;88
(suppl 1):3848
7. Cloutier MM, Wakeeld DB. Translation of a pediatric asthmamanagement program into a community in Connecticut. Pediatrics.
2011;127(1):1118
8. Stout JW, Smith K, Zhou C, et al. Learning from a distance:
effectiveness of online spirometry training in improving asthma
care. Acad Pediatr. 2012;12(2):8895
470
Pediatrics in Review
18. Parker JM, Dillard TA, Phillips YY. Arm span-height relationships
in patients referred for spirometry. Am J Respir Crit Care Med.
1996;154(2, pt 1):533536
19. Ruppel GL. Manual of Pulmonary Function Testing. 9th ed. St Louis,
MO: Mosby/Elsievier; 2009.
14. Hsu KHK, Jenkins DE, Hsi BP, et al. Ventilatory functions of
normal children and young adultsMexican-American, white, and
black. I. Spirometry. J Pediatr. 1979;95(1):1423
15. Polgar G, Promadhat V. Pulmonary Function Testing in Children:
Techniques and Standards. Philadelphia, PA: WB Saunders; 1971
16. Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG Jr. Pulmonary
function between 6 and 18 years of age. Pediatr Pulmonol. 1993;15(2):7588
Vol. 35 No. 11
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471
PIR Quiz
1. An 8-year-old presents to your ofce with a prolonged cough. You perform spirometry, and
his initial forced expiratory volume in 1 second (FEV1) is 1.30 L. After use of an inhaled
bronchodilator, which of the following FEV1 results represents the most signicant positive
response?
A.
B.
C.
D.
E.
1.15
1.25
1.35
1.40
1.55
L.
L.
L.
L.
L.
2. Which of the following spirometry measurements reects the ow from the smaller
airways?
A.
B.
C.
D.
E.
3. To gather the most useful and accurate information from spirometry testing, the child
should perform the test at least 3 times and:
A.
B.
C.
D.
E.
The child should exhale slowly and steadily for a minimum of 10 seconds.
The child should exhale through the nose and mouth forcefully for 1 to 2 seconds.
The child should hyperventilate for 30 to 45 seconds before testing.
The FEV1 should increase by at least 12% each time.
The highest FEV1 and FVC values should not differ by more than 5%.
4. When interpreting spirometry results, the most likely condition causing diminished FEV1
and FEF25%75% and resulting in a ow-volume loop with a scooped-out appearance is:
A.
B.
C.
D.
E.
Asthma.
Pneumoconiosis.
Pulmonary brosis.
Scoliosis.
Vocal cord dysfunction.
5. Which of the following clinical conditions is most likely to cause the following ndings on
spirometry: a small but normal-shaped ow-volume loop and demonstration of increased
ratio of FEV1/FVC?
A.
B.
C.
D.
E.
472
Asthma.
Bronchiectasis.
Chronic obstructive pulmonary disease.
Muscular dystrophy.
Sarcoidosis.
Pediatrics in Review
REQUIREMENTS: Learners
can take Pediatrics in
Review quizzes and claim
credit online only at:
http://pedsinreview.org.
To successfully complete
2014 Pediatrics in Review
articles for AMA PRA
Category 1 CreditTM,
learners must
demonstrate a minimum
performance level of 60%
or higher on this
assessment, which
measures achievement of
the educational purpose
and/or objectives of this
activity. If you score less
than 60% on the
assessment, you will be
given additional
opportunities to answer
questions until an overall
60% or greater score is
achieved.
Appendix A
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Appendix A Continued.
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Appendix B
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Respiratory Failure
Phuong Vo, MD,* Virginia S. Kharasch, MD
*Division of Pediatric Pulmonary and Allergy, Boston Medical Center, Boston, MA
Practice Gap
The primary cause of cardiopulmonary arrest in children is unrecognized
respiratory failure. Clinicians must recognize respiratory failure in its
early stage of presentation and know the appropriate clinical
interventions.
Objectives
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EPIDEMIOLOGY
Infants and young children have a higher frequency of
respiratory failure. (3)(4) Approximately half of respiratory
failure cases are seen in the neonatal period, resulting from
complications of prematurity and transitioning to extrauterine life. In addition, developmental differences between
children and adults also explain the higher incidence. (1)
(3)(4) First, infants and young children have a smaller upper
airway, with the subglottic area being the narrowest. Any
inammatory process can result in airway narrowing and
subsequently in increased work of breathing. Second,
immature stages of lung growth and development present
with fewer numbers of alveoli, smaller intrathoracic airway
caliber with little cartilaginous support, and underdeveloped
collateral ventilation, predisposing infants to atelectasis.
Third, infant respiratory muscles have reduced type 1 muscle bers, specically the diaphragm, resulting in lower
respiratory tract muscle bulk and reserve. Fourth, the chest
wall is more compliant than in adults because of a less bony
thorax, compromising thoracic expansion, and may result in
accessory muscle use and paradoxical patterns of respiration.
Fifth, bradypnea, apnea, or tachypnea commonly results from
the immaturity of the respiratory center. All these factors
result in a higher metabolic demand per kilogram of body
weight, resulting in increased work of breathing and early
fatigue.
PATHOPHYSIOLOGY
Respiration involves the nervous, cardiovascular, musculoskeletal, and respiratory systems. The causes of respiratory
failure can come from any of these systems and are expansive. Common causes can be grouped based on underlying
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TABLE 1.
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Pediatrics in Review
mismatch, impairment of gas exchange at the alveolarcapillary membrane is observed in progressive cystic brosis
disease with pulmonary brosis and destruction. (8) Obstruction from infectious causes, foreign-body aspiration, burn
injuries, anaphylaxis, or decreased muscle tone from depressed consciousness or neuromuscular disorders can
result in complete or partial airway obstruction. Complete
obstruction causes asphyxia, where the lungs are not ventilated but well perfused. Adequate airow is usually initially
observed in partial obstruction. As airow obstruction increases from either a valvelike effect in foreign-body aspiration or airway inammation and mucous secretions,
respiratory failure can occur. (9) Central nervous system
disorders include congenital malformations, such as absent
corpus callosum; abnormal central control of respiration,
such as periodic breathing; apnea of prematurity; central
apnea; Ondine curse; acquired injuries, such as head trauma;
intracranial bleeding; hypoxic ischemic encephalopathy; and
cerebral palsy. In these conditions, respiratory efforts are
inadequate and hypoventilation or apnea ensues, resulting in
carbon dioxide retention and respiratory failure. (10)
CLINICAL PRESENTATIONS
The clinical presentations of respiratory failure depend on
the underlying cause and the level of hypoxemia and hypercapnia. Infants and children most commonly present with
increased work of breathing: tachypnea, grunting, nasal
aring, and retractions. (3)(11) These signs of increased
work of breathing are blunted in those with neuromuscular
disorders. These patients instead present with tachypnea
and shallow breathing without retractions.
Additional signs and symptoms of respiratory failure
may be observed, depending on the level of hypoxemia
and hypercapnia (Table 2). (4) Impending respiratory failure
can present as dyspnea, mood changes, disorientation,
pallor, or fatigue. With acute hypercapnia, ushing, agitation, restlessness, headache, and tachycardia can occur.
Children with chronic respiratory failure often present with
worsening hypercapnia and hypoxemia. Reduced consciousness or coma and depressed tendon reexes occur
with severe chronic carbon dioxide retention. Cyanosis,
polycythemia, cor pulmonale, and pulmonary hypertension
are complications of chronic hypoxemia.
TABLE 2.
HYPOXIA
HYPERCAPNIAa
Mild
Mild
None or depressed
efciency
Moderate
Flushed skin
Headaches
Moderate
Dyspnea
Tachypnea
Headaches, dizziness
Tachycardia
Fatigue
Dyspnea
Pallor
Muscle twitches,
depressed tendon
reexes
Tachycardia, cardiac
arrhythmias
Drowsiness, confusion
Hypertension
Mood changes: euphoria,
disorientation, or depression
Ataxia, tingling
Hypertension
Severe
Severe
Cyanosis
Papilledema
Coma
Hypotension
Bradycardia
Visual impairment
Loss of consciousness,
seizures, coma
a
In chronic hypercapnia, signs and symptoms of hypercapnia are
observed when PCO2 increases above baseline level.
muscular dystrophy) must be identied. (4) Additional factors, such as history of fevers, symptoms of respiratory
infection (cough, rhinorrhea, or nasal congestion), history
of seizures, head trauma, or possible exposures to sedatives,
must be noted. (3)(4)
For the physical examination, vital signs are very helpful
to indicate the severity of the respiratory failure. (3)(11)
Tachypnea is a sensitive indicator of respiratory disease.
Increased respiratory rate is one of the earliest compensatory mechanisms of respiratory failure. However, respiratory rates can be elevated during infancy, sleeping, eating,
and increased activity in healthy children. Heart rate also
increases to maintain adequate oxygen delivery. Blood pressure can be initially normal or high. When respiratory
failure is in the decompensated phase, low blood pressure
occurs. Pulse oximetry saturation estimates the oxygen
saturation of hemoglobin. A 90% oxygen saturation on
pulse oximetry correlates with a PaO2 of 60 mm Hg based
on the sigmoid shape of the oxyhemoglobin dissociation
curve (Figure 2). (6) Pulse oximetry measures only saturation. It does not measure oxygen content or delivery. Thus,
pulse oximetry has several limitations. The oxygen saturation can be falsely high with an elevated carboxyhemoglobin
level in a patient with carbon monoxide or methylene
chloride poisoning. (12) Carbon monoxide binds to hemoglobin with much greater afnity than oxygen, leading to
tissue hypoxia. It also causes a left shift of the oxyhemoglobin dissociation curve, thereby decreasing the release of the
oxygen and causing further tissue hypoxia. In a patient with
an elevated methemoglobin level, the pulse oximetry saturation tends to be overestimated. In patients with poor tissue
perfusion due to shock, hypovolemia, or hypothermia, the
pulse oximetry is unable to detect the oxygen saturation accurately; these patients may have falsely low oxygen saturation.
The initial step of the physical examination of respiratory
failure is assessing the work of breathing. (3)(11) One should
assess the respiratory rate and quality, keeping in mind agespecic norms. When tachypnea is accompanied by retractions, nasal aring, or grunting, respiratory support with
either noninvasive or invasive positive pressure is needed.
Bradypnea is often observed in respiratory center failure,
indicating the need for emergency respiratory intervention.
Bradypnea or hypoventilation is also observed in patients
with neuromuscular disorders. These patients have shallow
and ineffective breathing and usually do not present with
retractions. In these patients, spirometric measurements
with forced vital capacity less than 40% correlate with
carbon dioxide retention and nocturnal hypoventilation.
When assessing the respiratory rate, the chest wall should
also be inspected. Asymmetric chest expansion indicates
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DIAGNOSIS
Laboratory and radiographic studies are helpful in the assessment of respiratory failure and the monitoring of the
response to therapeutic management. However, emergency
respiratory support should be initiated when indicated and
not be delayed while awaiting results of diagnostic studies.
Laboratory studies, such as an arterial blood gas, endtidal carbon dioxide, oxygen saturation, a complete blood
cell count with differential, and renal and liver functions,
should be performed. The arterial blood gas accurately measures the extent of the gas exchange abnormality and conrms the type and chronicity of respiratory failure. (4)
Normal arterial blood gas values are as follows: pH 7.4
(reference range, 7.387.42); PO2, 80 to 100 mm Hg; PCO2, 35
to 45 mm Hg; oxygen saturation, 95% on room air; bicarbonate, 22 to 26 mEq/L; and base excess, 2 to 2 mEq/L. In
acute respiratory failure, PaO2 is less than 60 mm Hg, pH is
below 7.35, PaCO2 is greater than 50 mm Hg, and serum
bicarbonate concentration is low or normal. In chronic
carbon dioxide retention, carbon dioxide is increased, pH
TABLE 3.
MANAGEMENT
Early diagnosis, close monitoring, and timely intervention
are of utmost importance in a patient presenting with
respiratory distress. (3)(4) The primary cause of cardiopulmonary arrest in children is unrecognized respiratory failure. Interventions in a patient with respiratory failure range
from close monitoring and supplemental oxygen to full
respiratory support with mechanical ventilation. The initial
step in the treatment of a patient with respiratory failure is
rapid assessment of airway, breathing, and circulation to
determine whether the patient needs urgent intervention.
Indications for intubation and mechanical ventilation
include the patients inability to maintain an adequate
airway and protect the airway from aspiration, failure of
oxygenation and ventilation, and deteriorating status that
will lead to inability to maintain airway patency and normal
gas exchange.
The initial step and most basic airway management for
a patient in respiratory failure is bag-mask ventilation,
which allows for oxygenation and ventilation until a more
denitive airway can be established. Although the patient is
receiving bag-mask ventilation, necessary equipment (endotracheal tube, large-bore suction, beroptic scope, laryngoscope, carbon dioxide detector, and intubation drugs) can be
prepared for intubation. (4) When possible, intubation
should be performed by the most experienced medical
professional (emergency care personnel, critical care physicians, and anesthesiologists) to ensure successful intubation and to avoid multiple unsuccessful attempts. Failure to
CONDITION
pH
Paco2
BASE EXCESS
/[
Normal/slightly Y
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Summary
On the basis of research evidence, (1)(2) numerous diseases and
conditions can impair gas exchange, resulting in failure to meet
the bodys metabolic demands and leading to respiratory failure.
On the basis of consensus, (1)(2)(7)(8)(9)(10) the clinical
presentations of respiratory failure depend on the underlying
cause and the level of hypoxemia and hypercapnia. Early
diagnosis, close monitoring, and timely intervention are of
utmost importance.
On the basis of research evidence, (5)(14)(25) interventions range
from noninvasive methods, such as close monitoring and
supplemental oxygen, to full respiratory support with mechanical
ventilation and in extreme cases even the use of extracorporeal
membrane oxygenation.
ACKNOWLEDGMENT
References
1. Gutierrez JA, Duke T, Henning R, South M. Respiratory failure and
acute respiratory distress syndrome. In: Taussig LMLL, ed. Pediatric
Respiratory Medicine. Vol 2. Philadelphia, PA: Mosby Elsevier;
2008:253274
2. Roussos C, Koutsoukou A. Respiratory failure. Eur Respir J Suppl.
2003;47(suppl 47):3s14s
3. Hammer J. Acute respiratory failure in children. Paediatr Respir Rev.
2013;14(2):6469
4. Nitu ME, Eigen H. Respiratory failure. Pediatr Rev. 2009;30
(12):470478.
5. Tobin MJ, Laghi F, Jubran A. Ventilatory Failure, Ventilator Support,
and Ventilator Weaning. Comprehensive Physiology. Hoboken, NJ:
John Wiley & Sons Inc.; 2012
6. Leff AR, Schumacker PT. Respiratory Physiology. Philadelphia, PA:
WB Saunders Company; 1993
27. OBrien JE, Haley SM, Dumas HM, et al. Outcomes of post-acute
hospital episodes for young children requiring airway support. Dev
Neurorehabil. 2007;10(3):241247
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Pediatrics in Review
28. OBrien JE, Dumas HM, Haley SM, et al. Ventilator weaning
outcomes in chronic respiratory failure in children. Int J Rehabil Res.
2007;30(2):171174
29. OBrien JE, Birnkrant DJ, Dumas HM, et al. Weaning children from
mechanical ventilation in a post-acute care setting. Pediatr Rehabil.
2006;9(4):365372
PIR Quiz
1. You are seeing 2 brothers ages 2 months and 6 years, respectively, for upper respiratory
tract infection. Rapid antigen testing suggests infection with respiratory syncytial virus.
Which of the following factors is most important in placing the younger sibling at greater
risk of developing respiratory decompensation compared with his older brother?
A.
B.
C.
D.
E.
3. A 10-month-old girl presents with poor feeding, fever, cough, and respiratory difculty for
the last 2 days. Physical examination reveals axillary temperature of 38.9C, respiratory rate
of 65 breaths per minute, and heart rate of 170 beats per minute. Respirations are labored
with nasal aring and intercostal retractions. Auscultation of chest reveals diffuse crackles
(rales) and wheezing throughout the chest. There are alternating periods of drowsiness
and agitation. Use of 100% oxygen at 15 L/min via a nonrebreather face mask is initiated.
Pulse oximetry recording reveals 93% oxygen saturation. Which of the following will
prompt you to proceed with tracheal intubation and mechanical support of respiration?
A. Arterial blood gas revealing PaO2 less than 60 mm Hg on currently administered
oxygen.
B. Arterial blood gas revealing pH less than 7.25 and PCO2 less than 60 mm Hg.
C. Chest radiograph revealing diffuse alveolar interstitial inltrates.
D. Lack of improvement after a trial of nebulized albuterol inhalation.
E. No new information is necessary, so the patient should undergo tracheal intubation and mechanical support of respiration now.
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4. A 12-year-old boy presents with tingling, numbness, and weakness of his lower extremities
for 1 day. The weakness has gradually progressed, and now he is unable to walk. Physical
examination reveals a comfortable-appearing child with normal sensorium. He is afebrile,
with a respiratory rate of 18 breaths per minute and a heart rate of 74 beats per minute.
Respiratory pattern appears normal. He has sensory loss to pinprick up to the
midabdomen. He has decreased muscle strength: grade II/V in the lower extremities and
IV/V in the muscles of the hand. He appears to have normal strength in his shoulders and
arms. He has good gag and cough reexes. Deep tendon reexes are absent in the lower
extremities and diminished in the upper extremities. The rest of his physical examination
ndings are normal. Which of the following is the best method of determining need for
assisted ventilation?
A.
B.
C.
D.
E.
5. A 16-year-old girl with cystic brosis is admitted for low-grade fever, productive cough,
and shortness of breath. She is being followed up in the clinic for advancing lung disease.
Her baseline vital capacity is 40% of normal. Vital signs on presentation are as follows:
axillary temperature, 38.5C; pulse, 100 beats per minute; and respirations, 24 breaths per
minute. She has nasal aring, intercostal retractions, and diffuse bilateral wheezes and
crackles (rales) on chest auscultation. She is appropriately interactive. Her pulse oximetry
oxygen hemoglobin saturation on 30% oxygen, which she receives at home, is 85%. Her
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arterial blood gas reveals the following: pH, 7.28; PCO2, 62 mm Hg; and PO2, 55 mm Hg. Highow nasal cannula (15 L/min) with 100% oxygen is initiated. Fifteen minutes later, the
patient becomes unresponsive with shallow respirations at rate of 10 breaths per minute;
lung examination ndings are unchanged. A subsequent arterial blood gas determination
reveals the following: pH, 7.08; PCO2, 110 mm Hg; and PO2, 102 mm Hg. Which of the
following is the most likely explanation of the change in this childs worsened clinical state?
A.
B.
C.
D.
E.
486
Bilateral pneumothoraces.
Cerebral edema.
Exacerbation of cor pulmonale.
Respiratory muscle fatigue.
Suppression of peripheral chemoreceptors.
Pediatrics in Review
THE CASE
1
2
3
CASE 1 PRESENTATION
EDITORS NOTE
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presentations and discussions. Please use
the Submit and Track My Manuscript link
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AUTHOR DISCLOSURE Drs Vander Schaaf,
Potisek, Puri, Schlaudecker, Newman, Notario,
and Nagpal have disclosed no nancial
relationships relevant to this article. This
commentary does not contain a discussion of
an unapproved/investigative use of
a commercial product/device.
CASE 1 DISCUSSION
Abdominal ultrasonography revealed a long segment of abdominal aortic narrowing,
involving the mesenteric and renal arteries (initial renal ultrasonography result was
interpreted as normal), consistent with a diagnosis of midaortic syndrome (MAS).
Abdominal magnetic resonance angiography (MRA) conrms this diagnosis.
Pediatric hypertension affects roughly 5% of all children. Typical symptoms
include epistaxis, headaches, blurred vision, and vomiting; however, hypertension
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Differential Diagnosis
Epistaxis is commonly encountered by the pediatrician and is
typically anterior or posterior in origin. Anterior nosebleeds
account for most nosebleeds because of the highly vascular
Kiesselbach plexus in this region. Anterior nosebleeds are
typically caused by direct trauma, foreign bodies, mucosal
dryness, infection, or irritants. Posterior nosebleeds are less
common and may be the result of signicant nasal trauma or
potentially a tumor. Systemic causes include bleeding disorders, vasculitis, or hypertension as was found in our patient.
Worrisome ndings concerning nosebleeds are recurrent
episodes and episodes refractory to routine management.
The Condition
MAS is an uncommon cause of renovascular hypertension
in children. It results from narrowing of the abdominal
aorta, typically involving the renal arteries and other visceral
branches. Most cases of MAS are primarily idiopathic.
However, it may be associated with underlying conditions,
such as neurobromatosis type I, mucopolysaccharidosis,
William syndrome, Alagille syndrome, giant cell arteritis, or
congenital rubella. Hypertension is present in most MAS
cases. Claudication, oliguric renal failure, and intestinal
ischemia occur infrequently. The classic diagnostic triad
consists of an abdominal bruit, diminished or absent femoral pulses, and a discrepancy between blood pressures of
the upper and lower extremities. The physical examination
ndings of diminished femoral pulses and blood pressure
discrepancy between the upper and lower extremities can be
seen in coarctation of the aorta; however, echocardiography
typically detects this condition and is isolated to the aorta.
Once the diagnosis of MAS is suspected, MRA can conrm the diagnosis, with angiography remaining the gold
standard. Aortic narrowing may also be seen on computed
tomography angiography, abdominal ultrasonography, or
echocardiography during the evaluation of hypertension. If
MAS is suspected to be secondary, then a genetic evaluation
should be considered to evaluate the patient for the potential
underlying conditions mentioned above. In addition, evaluating for an inammatory state by obtaining an erythrocyte
sedimentation rate and C-reactive protein may help suggest
giant cell arteritis as a cause of MAS.
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Pediatrics in Review
Management
Hypertension secondary to MAS is typically severe and often
requires numerous antihypertensive medications and/or
surgical correction. Although hypertension can be controlled with several antihypertensive medications, surgery
is the denitive treatment. Surgery is often indicated for
unresponsive hypertension to medical therapy, claudication,
intestinal ischemia, or when the survival of the kidney is in
jeopardy. The decision for timing of surgical intervention is
often case dependent. Most cases are managed by a singlestaged aorto-aortic bypass of the diseased segment of the aorta
along with a surgical revascularization procedure of the renal
and splanchnic arteries as required.
Patient Course
On arrival, antihypertensive therapy was initiated for our patient. He was initially administered a nicardipine drip and
clonidine patch with the goal of maintaining a higher systemic
blood pressure to ensure adequate perfusion of his kidneys in
the setting of acute kidney injury. Unfortunately, the patient
became oliguric and developed progressively worsening renal
failure, ultimately requiring hemodialysis. He subsequently
developed respiratory failure and was intubated. After identifying MAS as the underlying cause of his hypertension, he was
transferred to a facility experienced in surgical correction of
this condition and underwent bilateral renal revascularization.
Two months after surgical repair, he is normotensive and not
taking any antihypertensive medications.
CASE 2 PRESENTATION
A 5-year-old boy is referred for a signicantly elevated white
blood cell count of 40,000/mL (40.0 109/L), with 76%
eosinophils (absolute eosinophil count of 30,400 /mL [30.4
CASE 2 DISCUSSION
An infectious diseases consultant recommended serologic
testing for Toxocara and ophthalmologic examination by
slitlamp to rule out ophthalmologic larva migrans (OLM).
The Toxocara serologic test (IgG by enzyme-linked immunosorbent assay) result was positive, with titers of 0.304
optical density (OD) at presentation (reference range,
00.299 OD). Ophthalmologic examination did not reveal
evidence of OLM.
Differential Diagnosis
The initial differential diagnoses in a child presenting with
severe hypereosinophilia includes neoplasm (including acute
The Condition
Eosinophilia is dened as eosinophil percentage greater
than 3% to 5% in the peripheral blood, with severity corresponding to absolute eosinophil count: mild, eosinophil
count of 600 to 1500/mL (1.5 109/L); moderate, eosinophil
count of 1500 to 5000/mL (1.55.0 109/L); and severe,
eosinophil count greater than 5000/mL (>5.0 109/L).
Primary eosinophilia may be due to various myeloid and
lymphoid neoplasms. However, secondary eosinophilia, due
to infections and other systemic diseases, such as collagen
vascular disorders, pulmonary eosinophilic diseases, allergic
disorders, and metabolic diseases, must be excluded rst.
Toxocariasis is a syndrome caused by the nematode
Toxocara canis or Toxocara cati. The dog and the cat are
the denitive hosts for T canis and T cati, respectively. Eggs
are shed in stool by the animal, become infective after
approximately 3 weeks (after embryonation), and remain
infective for several years in the environment. After ingestion by dogs or cats, the eggs hatch and the larvae penetrate
the gut wall; migrate through the lungs, the bronchial tree,
and the esophagus; and develop into adults in the small
intestine, from where they are shed in stool. Humans are
the unintentional hosts. Transmission is fecal-oral, by ingestion of the eggs or larvae, through contaminated hands or
other objects, or by ingestion of contaminated soil.
Toxocariasis is classically characterized by eosinophilia,
hepatomegaly, fever, and hyperglobulinemia due to the
systemic penetration of the worm larvae. Toxocariasis is
now formally classied into the classic systemic form, compartmentalized (neurologic larva migrans), or OLM, covert
and asymptomatic forms. Several authors have reported
signicant prevalence rates of asymptomatic infection, ranging from 5% in the white pediatric population to 25% in the
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Patient Course
Our patients condition may be classied into either an
asymptomatic or covert form based on his symptoms of
abdominal pain. The signicant eosinophilia and the high
titers of anti-Toxocara antibodies prompted treatment to
prevent complications. He was prescribed mebendazole
therapy, 100 mg twice daily for 5 days, because albendazole
was not available at his pharmacy. A follow-up white blood
cell count 4 weeks later was signicantly improved at
10,000/mL (10.0 109/L), with 22% eosinophils and an
absolute eosinophil count of 2230//mL (22.3 109/L).
Follow-up Toxocara antibody levels were elevated at 0.585
OD; however, his complete blood cell count continued to
normalize. Most recently, his lead level was 9.3 mg/dL (0.45
mmol/L), and the complete blood cell count was signicant
for a white blood cell count of 9100//mL (9.1 109/L), with
13% eosinophils (absolute erythrocyte count of 1180//mL
[11.8 109/L]), 28% lymphocytes, and 58% neutrophils.
We never positively identied the source of the infection
but strongly suspected the sandbox at the daycare. The cats
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Pediatrics in Review
getting into it were strays, and the family and the health
department tried to convince the owner to cover the sandbox
when not in use, but without effect. Ultimately, the children
stopped going to that daycare. The pets were never tested or
treated. Unfortunately, the health department jurisdiction
where the case occurred has a limited budget for enforcement activities related to environmental health.
CASE 3 PRESENTATION
A 3-month-old full-term girl with trisomy 21 presents to the
gastroenterology clinic with progressive feeding intolerance. For the past 3 weeks, she has had large nonbloody
spit-ups after every feed, either formula colored or light
brown in appearance. She has a normal appetite and does
not appear to be distressed after spit-ups. Her parents report
that she previously tolerated 3 oz of formula every 3 hours.
She has been stooling regularly without diarrhea and has
no other signs of illness. Birth weight was 3.85 kg (80th
percentile). She has a history of a small ventricular septal
defect and congenital bilateral clubfoot.
Physical examination reveals a well-appearing girl with
typical Down syndrome dysmorphic features. Her temperature is 37.2C, pulse is 89 beats per minute, respiratory rate
is 22 breaths per minute, blood pressure is 97/56 mm Hg,
and oxygen saturation is 97% on room air. Her perfusion is
normal. She currently weighs 3.93 kg (less than the third
percentile), her length is 57.5 cm (25th percentile), and her
head circumference is 39 cm (25th percentile). She has
normal heart sounds with a 2/6 systolic murmur over the
left sternal border. Her abdomen is soft, nondistended, and
nontender with normal bowel sounds. There are no abdominal masses or hepatomegaly. She has normal female external genitalia without lesions or hernias.
The result of a basic electrolyte panel is normal. A pyloric
ultrasonography result is normal. An upper gastrointestinal
CASE 3 DISCUSSION
Exploratory laparotomy revealed an annular pancreas, causing extrinsic duodenal compression. The patient underwent
duodenal duodenostomy from which she recovered well and
subsequently tolerated oral feeds.
The Condition
Annular pancreas is a relatively rare congenital condition,
with an incidence of 1 in 2000 live births. In 70% of cases,
annular pancreas is associated with other anomalies, such as
esophageal atresia, imperforate anus, congenital heart disease, and malrotation. Exact embryonal origins are unclear,
but the leading theory is that it results from aberrant rotation
of the ventral portion of the pancreas, preventing its fusion
with the dorsal portion. This causes wrapping of the pancreas 270 around the duodenum, typically at the second
portion as the duodenum descends in the abdomen.
Most patients with annular pancreas remain asymptomatic through their lifetime. However, of those children who
are symptomatic, more than two-thirds present as infants
with signs of obstruction, including bilious emesis, feeding
intolerance, and abdominal distension. When presenting in
later childhood and adulthood, patients experience symptoms
of peptic ulcer disease, duodenal obstruction, or pancreatitis.
Imaging studies of symptomatic infants, such as abdominal radiography, may reveal the classic double bubble sign
consistent with duodenal obstruction. An upper GI tract
series can reveal associated ndings, such as a transition
point between the rst and second parts of the duodenum.
Endoscopic retrograde cholangiopancreatography, magnetic
resonance cholangiopancreatography, and endoscopic ultrasonography are more recent additional modalities that can
be used to diagnose annular pancreas. The gold standard of
diagnosis is exploratory laparoscopy or laparotomy.
Management
The rst step in treating a patient with an apparent upper
GI tract obstruction is to provide gastric decompression
through the placement of a nasogastric tube. Intravenous
rehydration and correction of any electrolyte abnormalities
should be performed. Surgical repair is the ultimate treatment for patients with annular pancreas to relieve the
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Pediatrics in Review
Brief
in
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Childrens Hospital at Monteore, Albert Einstein College of Medicine,
Bronx, NY
Within the last 60 years, pediatric hepatology has seen many advances in improvement in timely diagnosis and management of chronic liver disease and also
in liver transplantation. Growth failure and malnutrition have always been important factors in the treatment of children with liver disease, specically cholestatic liver diseases. The liver has a central function in nutrient metabolism, and
the abnormalities seen in chronic liver disease result in nutritional and metabolic
deciencies. Nutritional needs are dependent on the type of liver disease, age of the
patient, and whether the disease is acute or chronic. In the setting of acute liver
disease, such as acute viral hepatitis, malnutrition is unusual; however, in fulminant liver failure, nutritional modications are needed to manage hepatic encephalopathy. Chronic liver disease may be cholestatic or noncholestatic and in most
instances is associated with malnutrition.
Cholestatic injury to the liver reects a diverse group of diseases, resulting
from biliary obstruction, disorders of bile synthesis or transport, metabolic and
endocrine disorders, infections, and toxic effects. The most common is biliary
atresia, occurring in approximately 1 of 10,000 live births; it is the most common
indication for liver transplantation in children. Patients have relatively progressive
hepatic disease and, often, poor nutritional status, making preoperative management of malnutrition a challenge.
Malnutrition is a negative prognostic indicator of overall survival, and the inability
to improve nutritional status before surgery increases the risk of postoperative complications and mortality. Adequate nutrition allows for growth, improved immunologic status, and improved transplantation outcomes.
Nutritional status in the setting of liver disease can be difcult to assess. Weight
alone is not a sufcient marker for nutritional status, especially if the patient has
ascites or organomegaly: uid retention and a disproportionately large organ may
result in substantial weight gain, whereas the overall nutritional status is actually
poor. The ascites and organomegaly, as well as portal hypertension, can also
contribute to poor oral tolerance, furthering the failure to gain appropriate weight
for age and preventing the often needed catch-up weight gain. Although serial
abdominal circumference measurement may aid in determining whether weight
gain is secondary to ascites, it is an imprecise way of differentiating true weight
gain from uid gain. More accurate measures include triceps skinfolds and
middle upper arm circumference measurements, with standards for age available
from the World Health Organization. These measurements, however, require
calipers and training in proper technique. Peripheral edema is a potential cause of
overestimation of both measures and if present needs to be considered.
Both the childs age and the specic disease affecting the liver contribute to the
issues of nutrition and growth facing each patient. Assessment and support are
key components of effective care, which is best performed by a team of physicians
Vol. 35 No. 11
NOVEMBER 2014
493
494
Pediatrics in Review
although increasing total fat intake increases overall fat absorption, it will also lead to increases in diarrhea and steatorrhea. Medium chain triglycerides (MCTs) are a readily
available source of energy and are absorbed directly from
the venous blood without the need for bile and emulsication. Supplying 30% to 70% of total fat as MCTs provides
adequate fat calories, reduces malabsorption of fat and steatorrhea, and improves weight gain. However, providing all
fat calories as MCTs can lead to essential fatty acid (EFA)
deciency. The EFAs are linoleic acid and a-linolenic acid,
which are not produced by the body but are necessary for
production of long-chain polyunsaturated fatty acids and are
important in brain and eye development. To prevent deciency, approximately 10% of energy should be provided as
supplemental EFAs, with a ratio of linoleic to a-linolenic acid
of 1:5 to 1:15. Certain dietary oils (walnut, canola, sunower,
and soybean), as well as sh oils and egg yolks, can be used in
oral and enteral tube feeding to provide additional fat calories.
Formulas with adequate amounts of MCTs as a proportion of
total fat calories are recommended for infants with cholestatic
liver disease. Older children may benet from MCT oil supplementation to their meals.
Amino acid metabolism is altered in chronic liver disease, with branched-chain amino acid levels decreased and
aromatic amino acid levels increased. Branched-chain amino
acid supplementation may reduce protein catabolism, improve nitrogen retention, and improve protein synthesis.
Children with chronic liver disease typically require 2 to
3 g/kg daily as the protein intake sufcient for growth. With
hepatocyte loss, liver insufciency, and portosystemic shunting, protein intake can lead to hyperammonia. Nonetheless,
protein restriction should not be used to reduce ammonia
levels; rather, hyperammonemia should be treated with
lactulose or sodium benzoate.
Fat malabsorption can lead to deciency of the fat soluble
vitamins (A, D, E, and K). Other vitamins and minerals can
be decient as well, and proper monitoring is important.
Supplementation, available in an oral water soluble form,
with vitamins A, D, E, and K is recommended for all children
with cholestatic liver disease (Table). Water soluble vitamins
should be supplemented at twice the recommended daily
allowance because of the risk of altered metabolism by the
diseased liver. Trace elements (calcium, zinc, magnesium, and
selenium) should be supplemented based on the patients
plasma levels. Careful attention should be paid to the potential
for copper toxicity in the setting of cholestasis, and serum
levels should be drawn during nutritional assessments. Iron
TABLE.
VITAMIN SOURCE
DEFICIENCY
TOXIC EFFECTS
Night blindness,
xerophthalmia
Liver brosis,
Serum retinol,
hypercalcemia,
serum retinol/RBP
pseudotumor cerebri,
ratio, retinal dose
painful bone lesions
response test,
liver retinol level
5000-25,000 U/d,
coadministered
with TPGS for
improved
absorption
Hypocalcemia,
hypophosphatemia,
muscle hypotonia,
and rickets
Hypercalcemia and
pseudotumor
cerebri
25-Hydroxyvitamin
D serum levels
(measure serum
ionized calcium
and phosphorus)
400 IU/d,
25-hydroxyvitamin
D3 preferred
Supplementation
should be given
with adequate
calcium and
phosphorus
25-Hydroxyvitamin
D serum levels
>20 ng/mL
Poor nerve
conduction,
leading to hypo- or
areexia, ataxia,
peripheral
neuropathy,
and myopathy
Vision loss
Hemolytic anemia
Impaired neutrophil
chemotaxis
Vitamin E (serum
Oral TPGS-E
tocopherol)/total
supplementation
lipid ratio
(>0.8 mg/g normal)
Dry skin
Possible immune
dysfunction
MEASUREMENT
Hemorrhagic disease
Vitamin K Dietary source: vitamin
K1 (phylloquinone)
green leafy vegetables,
dairy products, and liver
Synthesis of uncarboxylated
Enteric bacteria derived:
proteins (coagulation
vitamin K2
(menaquinones)
factors: II, VII, IX, X,
and protein C and S)
SUPPLEMENTATION
PIVKA II assay
(proteins induced
in vitamin
K absence)
Intravenous,
intramuscular,
or subcutaneous
administration
may be necessary
Abbreviations: INR=international normalized ratio; PIVKA=Proteins Induced by Vitamin K Absence; RBP=retinal-binding protein; TPGS=D-a-tocopheryl
polyethylene glycol succinate; TPGS-E=vitamin E D-a-tocopheryl polyethylene glycol succinate.
Vol. 35 No. 11
NOVEMBER 2014
495
feeding can be performed at home overnight as supplementation to daytime oral feeds, which should be encouraged to
maintain feeding skills. Gastrostomy feeding is not a route
of choice because placement of the gastrostomy tube can be
complicated by organomegaly, ascites, and bleeding risks.
Used only when enteral feeding cannot meet a childs
nutritional needs, parenteral nutrition is a last resort that
comes with its own sets of concerns: the risk of sepsis
from central catheter infections and additional parenteral
nutritionrelated toxic effects to the liver.
Malnutrition and growth failure in children with liver
disease are multifactorial. Despite advances in management, malnutrition has remained a challenge, and nutritional support is a central goal in the care of these children.
Malnutrition has been associated with poor outcomes.
Assessment of nutritional status is complicated by changes
in body habitus and uid retention. Children with chronic
cholestatic liver disease have increased overall caloric needs,
as well as specic needs in the composition of their intake of
macromolecules. Attention must also be paid to micronutrient and vitamin deciencies. Care is best provided within
496
Pediatrics in Review
Brief
in
Bacterial Tracheitis
Connie Y. Kuo, MD, Sanjay R. Parikh, MD
Department of Otolaryngology, Seattle Childrens Hospital, Seattle, WA
Vol. 35 No. 11
NOVEMBER 2014
497
498
Pediatrics in Review
aeruginosa, and other gram-negative organisms. Antibiotic treatment should again be directed at the most common pathogens
for 7 to 10 days, taking into account the possibility of
multidrug-resistant organisms. If feasible, serial surveillance
of endotracheal aspirate specimens can identify multidrugresistant pathogens and help tailor antibiotic therapy.
The risk of VAT peaks at approximately 4 days after intubation, with an estimated incidence of 2% to 11%. The onset of
bacterial tracheitis in children with long-standing tracheotomies
is less predictable, with a reported incidence of less than 1%.
In general, tracheotomy-associated tracheitis is not aggressive
and, if there is close follow-up, can be treated in the outpatient setting with oral antibiotics, topical ciprooxacin and
dexamethasone, or tobramycin and dexamethasone drops
directed into the tracheotomy for several days. Recurrence
of tracheitis is more common in children with a long-term
tracheotomy.
During the past several decades, the incidence, diagnosis, and management of bacterial tracheitis have been
inuenced by new vaccines and by the heightened awareness among physicians of the alarmingly high morbidity
associated with delayed recognition. Despite its low incidence, clinicians must consider the possibility of bacterial
tracheitis in any patient with acute respiratory decompensation
Vol. 35 No. 11
NOVEMBER 2014
499
PRESENTATION
On a routine postdelivery checkup, an 8-day-old boy is found to have new onset of
pallor and hypotonia. Physical examination reveals pudgy cheeks, micrognathia
and retrognathia, and white, sparse hair (Figure 1).
The pregnancy was unremarkable, with all ultrasonographic ndings
described as normal. He was the rst and only child of a young and unrelated
couple. The father has rheumatoid arthritis and ankylosing spondylitis. The
patient was born at 39 weeks of gestation, weighing 2990 g and having Apgar
scores of 9/10 (1 and 5 minutes, respectively). Delivery was by caesarian section
because of pelvic-fetal incompatibility.
Vol. 35 No. 11
NOVEMBER 2014
e53
DIAGNOSIS
The clinical diagnosis of Menkes disease was based on the
typical hair changes associated with hypotonia, pale skin,
and signs of spontaneous fractures in the neonatal period.
The diagnosis was conrmed by the MRA results (elongated
and tortuous brain vessels), by pili torti (attened hair shafts
with clusters of narrow twists at irregular intervals) revealed
by electronic microscopy (Figure 4), and by the detection of
a new mutation of the ATP7A gene in the molecular study
from exons 18 to 23.
DISCUSSION
Menkes kinky hair disease is an X-linked recessive trait
condition that affects males. Female carriers generally do
not manifest symptoms unless unusual genetic circumstances are present. Menkes kinky hair disease is rare, with
an estimated incidence of 1 case in 250,000 live births
(1 case in 50,000100,000 in Australia).
e54
Pediatrics in Review
TREATMENT
If given in the rst months of life, copper histidinate in
a dose of 50 to 150 mg/kg per day, injected subcutaneously,
can increase life expectancy from the expected life span of 3
to 13 years, at least in some patients. In addition, this
treatment has an effect on neurologic manifestations and
neurodevelopmental outcome, which are improved in
approximately 30% of the patients. Nevertheless, in approximately 50% of the patients, this therapeutic approach has
not proven to be of any signicant benet, even when started
early in life. Oral administration is not an option because of
low intestinal copper absorption.
DISEASE COURSE
Menkes disease is a very severe disease with a high mortality
rate. Low body copper and ceruloplasmin levels have a signicant effect on several organs, and patients usually die of
pneumonia, although some patients die suddenly in the
absence of any apparent acute medical condition. Whereas
most patients exhibit a severe classic form, approximately
9% may have a milder form of Menkes disease called
occipital horn syndrome. Parents of children who have this
disorder are advised to have prenatal genetic counseling
because the risk of the condition being present in future
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of Menkes disease includes
Ehlers-Danlos syndrome, Marfan syndrome, cutis laxa, mitochondrial disorders, osteogenesis imperfecta, and child
abuse.
PATIENT COURSE
The patient started treatment with subcutaneous copper
histidinate in a dose of 50 mg/kg per day at age 2 months.
After 10 days of this treatment, copper levels (100 mg/dL [15.7
mmol/L]) and ceruloplasmin levels (17 mg/dL [170 mg/L])
were near normal. He developed seizures characterized by
masticatory movements, hypersalivation, eye deviation,
and limb muscle contractions. Electroencephalography
revealed persistent paroxysmal activity, particularly during
sleep. His seizures continued despite being given sodium
valproate, phenobarbital, and clonazepam. Seizures were
nally controlled with intravenous methylprednisolone.
His prognosis is poor because symptoms started in the
neonatal period and his ATP7A deletion is very long (from
exon 18 to 23).
Vol. 35 No. 11
NOVEMBER 2014
e55
Summary
A hypotonic newborn or infant with pale skin and sparse, friable,
hypopigmented, or depigmented hair should have his copper and
ceruloplasmin plasma levels evaluated because this is the usual clinical
presentation of Menkes disease. Menkes disease is an X-linked
recessive disease caused by a defect in the ATP7A gene, identied in
95% to 98% of the cases. Identifying the mutation conrms the
diagnosis and allows for prenatal counseling and diagnosis in a future
pregnancy. When administered within the rst few months of life,
copper histidinate, given subcutaneously in a dose of 50 to 150 mg/kg
per day, appears to be effective not only by increasing life expectancy
from 3 to 13 years but also by improving neurologic symptoms and
neurodevelopmental outcomes in approximately 30% of the patients.
e56
Pediatrics in Review
Suggested Reading
Bindu PS, Taly AB, Kothari S, et al. Electro-clinical features and
magnetic resonance imaging correlates in Menkes disease. Brain
Dev. 2013;35(5):398405
Kaler SG. ATP7A-related copper transport diseases-emerging
concepts and future trends. Nat Rev Neurol. 2011;7(1):
1529
Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport
disorders: biochemical mechanisms, diagnosis, and treatment.
Curr Drug Metab. 2012;13(3):237250
Tang J, Donsante A, Desai V, Patronas N, Kaler SG. Clinical outcomes in
Menkes disease patients with a copper-responsive ATP7A
mutation, G727R. Mol Genet Metab. 2008;95(3):174181
Tmer Z. An overview and update of ATP7A mutations leading to
Menkes disease and occipital horn syndrome. Hum Mutat.
2013;34(3):417429
PRESENTATION
A 6-month-old white boy presents to the emergency department for pain on
manipulation of his right lower extremity. His father reports lifting him off the
couch the day before when the boys right leg had become stuck in a space
between the cushions. After his father pulled his leg free, the child appeared to be
uncomfortable, but his symptoms rapidly resolved. No other history of trauma is
reported. However, today the patient was seen crying when his older sister was
pulling on his right leg.
The patients perinatal history is unremarkable. The medical history is
signicant only for strabismus, which was recently noted by his pediatrician.
He is being formula fed and takes rice cereals and early-stage baby foods. He takes
no medications. Both height and weight are tracking at the 90th percentile. He is
meeting all developmental milestones.
On physical examination, the child is alert and interactive. His examination
ndings are notable for a blue hue to his sclerae that has been present since birth
(Figure 1). He has pain to palpation over the right anterior tibia and refuses to bear
weight on that leg. Skin examination reveals no ecchymoses, lacerations, marks,
or abrasions. He has no other areas of tenderness, and the remainder of his
physical examination ndings are normal. Intentional trauma is a concern given
the minimal force of the reported mechanism of injury that led to this childs
fracture. Radiographs in the emergency department reveal an oblique, nondisplaced, middiaphyseal right tibial fracture (Figure 2).
Genetics testing reveals the underlying diagnosis.
Figure 1. Recent photograph of the child at age 2 years. The blue hue to his sclerae has been
present since birth.
*Department of Pediatrics, Tripler Army Medical Center, Honolulu, HI.
Vol. 35 No. 11
NOVEMBER 2014
e57
DIFFERENTIAL DIAGNOSIS
Figure 2. Oblique, nondisplaced, middiaphyseal right tibial fracture.
DIAGNOSIS
Because of this patients blue sclerae and presentation with
a fracture, genetic testing is performed. COL1A1 and
COL1A2 sequencing analysis conrms a mutation
(c.3162delT) in COL1A1, the gene that encodes the a1-chain
of type 1 collagen. This child is diagnosed as having osteogenesis imperfecta (OI) type 1.
DISCUSSION
Nine subtypes of OI have been described. In type I OI, an
autosomal dominant mutation in the COL1A1 gene causes
premature termination of pro-a1-collagen messenger RNA
(mRNA). This abnormal mRNA is rapidly degraded by
nonsense mediated decay, and as a result, patients with
type I OI have only 50% of the normal procollagen mRNA,
generated from the unaffected allele. As a result of this
decreased production of type 1 collagen, patients with type I
OI have increased bone fragility and an increased rate of
fractures. Patients with type I OI can have slightly short
stature and blue sclerae. They commonly have vertebral
fractures but usually have an absence of major bone deformities. Hearing loss can develop, usually after age 10
years. Dentogenesis imperfecta is typically absent in type I
OI, but kyphosis and scoliosis may develop over time.
e58
Pediatrics in Review
MANAGEMENT
Treatment of OI involves a coordinated multidisciplinary
approach that consists of physical and occupational therapy,
orthopedic surgical interventions, and medications to reduce
fracture rates, prevent long-bone deformities and scoliosis,
PROGNOSIS
The prognosis for an individual with OI varies greatly,
depending on the number and severity of symptoms. Patients with type I (mild type) typically experience most of
their fractures before puberty. It is uncommon to have bone
deformities, and they are usually of normal or near-normal
stature. Hearing loss is a major concern.
PATIENT COURSE
This child had 4 additional fractures in his feet and legs
during the next 2 years. He was then referred to the pediatric
endocrinology department at age 2 years. A bone density
scan revealed reduced bone mineral density of the lumbar
spine (z score 2.0) (Figure 3). His 25-hydroxyvitamin D
level was 20 ng/mL (50 nmol/L) (borderline for vitamin
D deciency), and treatment was initiated with vitamin D
(ergocalciferol) at 2000 IU/d. His 25-hydroxyvitamin D
level normalized to 35 ng/mL (87 nmol/L) within 2 months.
In addition, intravenous pamidronate treatment was initiated for 3 days every 3 months, and consideration is currently being given to placing intramedullary telescoping
rods in both lower extremities.
Figure 3. Bone mineral density of the lumbar spine was 0.361 g/cm2 at
age 2 years, demonstrating moderate osteopenia (z score 2.0).
Vol. 35 No. 11
NOVEMBER 2014
e59
Summary
Pediatricians play an important role in diagnosing OI as a cause of
fracture and may be asked to differentiate this uncommon
genetic diagnosis from intentional trauma and other causes of
fracture.
Early referral to a pediatric endocrinologist, physical therapist,
and orthopedic surgeon for the evaluation and treatment of low
bone mass and recurrent fractures is important because early
medical and surgical intervention may help to minimize the rate
of future fractures, even within the rst year of life.
Continued follow-up with physical and occupational therapy,
audiology testing, and regular evaluations of dental health are all
essential for children with OI.
e60
Pediatrics in Review
Suggested Reading
Rauch F, Glorieux FH. Osteogenesis imperfecta, current and future
medical treatment. Am J Med Genet C Semin Med Genet. 2005;139C
(1):3137
Ruck J, Dahan-Oliel N, Montpetit K, Rauch F, Fassier F. Fassier-Duval
femoral rodding in children with osteogenesis imperfecta receiving
bisphosphonates: functional outcomes at one year. J Child Orthop.
2011;5(3):217224
van Dijk FS, Cobben JM, Kariminejad A, et al. Osteogenesis
imperfecta: a review with clinical examples. Mol Syndromol.
2011;2(1):120
2015
AAP CME Schedule
THE BEST PEDIATRIC CME/CPD * FOR THE BEST PEDIATRIC CARE
JANUARY
FEBRUARY
Clinical Pediatric
MARCH
APRIL
Workshop on
Practical Pediatrics
CME Course
San Francisco, CA
May 22-24
Perinatal Practice
Strategies
Scottsdale, AZ
March 27-29
Practical Pediatrics
CME Course
Lake Tahoe, CA
January 29 - February 1
Neonatal/Perinatal
Practical Pediatrics
CME Course
Santa Fe, NM
April 24-26
Coding Seminar
Scottsdale, AZ
March 27
Register Online
www.aap.org/
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February 21-25
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October 24-27
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August 17-22
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April 25-28
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May 22-24
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CME Course
Orlando, FL
March 13-15
Hospital Medicine:
Caring for Newborns
and Children in the
Hospital Setting
San Diego, CA
January 16-18
MAY
DECEMBER
aeruginosa, and other gram-negative organisms. Antibiotic treatment should again be directed at the most common pathogens
for 7 to 10 days, taking into account the possibility of
multidrug-resistant organisms. If feasible, serial surveillance
of endotracheal aspirate specimens can identify multidrugresistant pathogens and help tailor antibiotic therapy.
The risk of VAT peaks at approximately 4 days after intubation, with an estimated incidence of 2% to 11%. The onset of
bacterial tracheitis in children with long-standing tracheotomies
is less predictable, with a reported incidence of less than 1%.
In general, tracheotomy-associated tracheitis is not aggressive
and, if there is close follow-up, can be treated in the outpatient setting with oral antibiotics, topical ciprooxacin and
dexamethasone, or tobramycin and dexamethasone drops
directed into the tracheotomy for several days. Recurrence
of tracheitis is more common in children with a long-term
tracheotomy.
During the past several decades, the incidence, diagnosis, and management of bacterial tracheitis have been
inuenced by new vaccines and by the heightened awareness among physicians of the alarmingly high morbidity
associated with delayed recognition. Despite its low incidence, clinicians must consider the possibility of bacterial
tracheitis in any patient with acute respiratory decompensation
Practical Pediatrics
CME Course
Nashville, TN
December 11-13
Pre-conference Session
October 23
Practical Pediatrics
CME Course
Chicago, IL
September 4-6
Practical Pediatrics
CME Course
Phoenix, AZ
November 13-15
Subspecialty/Section
CME Courses
Appropriate for the
pediatric subspecialist or
the general pediatrician
with a particular interest
in the topic.
The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
These activities have been approved for AMA PRA Category 1 Credit.
*Continuing Professional Development.
Vol. 35 No. 11
NOVEMBER 2014
499
PRESENTATION
On a routine postdelivery checkup, an 8-day-old boy is found to have new onset of
pallor and hypotonia. Physical examination reveals pudgy cheeks, micrognathia
and retrognathia, and white, sparse hair (Figure 1).
The pregnancy was unremarkable, with all ultrasonographic ndings
described as normal. He was the rst and only child of a young and unrelated
couple. The father has rheumatoid arthritis and ankylosing spondylitis. The
patient was born at 39 weeks of gestation, weighing 2990 g and having Apgar
scores of 9/10 (1 and 5 minutes, respectively). Delivery was by caesarian section
because of pelvic-fetal incompatibility.
Vol. 35 No. 11
NOVEMBER 2014
e53
DIAGNOSIS
The clinical diagnosis of Menkes disease was based on the
typical hair changes associated with hypotonia, pale skin,
and signs of spontaneous fractures in the neonatal period.
The diagnosis was conrmed by the MRA results (elongated
and tortuous brain vessels), by pili torti (attened hair shafts
with clusters of narrow twists at irregular intervals) revealed
by electronic microscopy (Figure 4), and by the detection of
a new mutation of the ATP7A gene in the molecular study
from exons 18 to 23.
DISCUSSION
Menkes kinky hair disease is an X-linked recessive trait
condition that affects males. Female carriers generally do
not manifest symptoms unless unusual genetic circumstances are present. Menkes kinky hair disease is rare, with
an estimated incidence of 1 case in 250,000 live births
(1 case in 50,000100,000 in Australia).
e54
Pediatrics in Review
TREATMENT
If given in the rst months of life, copper histidinate in
a dose of 50 to 150 mg/kg per day, injected subcutaneously,
can increase life expectancy from the expected life span of 3
to 13 years, at least in some patients. In addition, this
treatment has an effect on neurologic manifestations and
neurodevelopmental outcome, which are improved in
approximately 30% of the patients. Nevertheless, in approximately 50% of the patients, this therapeutic approach has
not proven to be of any signicant benet, even when started
early in life. Oral administration is not an option because of
low intestinal copper absorption.
DISEASE COURSE
Menkes disease is a very severe disease with a high mortality
rate. Low body copper and ceruloplasmin levels have a signicant effect on several organs, and patients usually die of
pneumonia, although some patients die suddenly in the
absence of any apparent acute medical condition. Whereas
most patients exhibit a severe classic form, approximately
9% may have a milder form of Menkes disease called
occipital horn syndrome. Parents of children who have this
disorder are advised to have prenatal genetic counseling
because the risk of the condition being present in future
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of Menkes disease includes
Ehlers-Danlos syndrome, Marfan syndrome, cutis laxa, mitochondrial disorders, osteogenesis imperfecta, and child
abuse.
PATIENT COURSE
The patient started treatment with subcutaneous copper
histidinate in a dose of 50 mg/kg per day at age 2 months.
After 10 days of this treatment, copper levels (100 mg/dL [15.7
mmol/L]) and ceruloplasmin levels (17 mg/dL [170 mg/L])
were near normal. He developed seizures characterized by
masticatory movements, hypersalivation, eye deviation,
and limb muscle contractions. Electroencephalography
revealed persistent paroxysmal activity, particularly during
sleep. His seizures continued despite being given sodium
valproate, phenobarbital, and clonazepam. Seizures were
nally controlled with intravenous methylprednisolone.
His prognosis is poor because symptoms started in the
neonatal period and his ATP7A deletion is very long (from
exon 18 to 23).
Vol. 35 No. 11
NOVEMBER 2014
e55
Summary
A hypotonic newborn or infant with pale skin and sparse, friable,
hypopigmented, or depigmented hair should have his copper and
ceruloplasmin plasma levels evaluated because this is the usual clinical
presentation of Menkes disease. Menkes disease is an X-linked
recessive disease caused by a defect in the ATP7A gene, identied in
95% to 98% of the cases. Identifying the mutation conrms the
diagnosis and allows for prenatal counseling and diagnosis in a future
pregnancy. When administered within the rst few months of life,
copper histidinate, given subcutaneously in a dose of 50 to 150 mg/kg
per day, appears to be effective not only by increasing life expectancy
from 3 to 13 years but also by improving neurologic symptoms and
neurodevelopmental outcomes in approximately 30% of the patients.
e56
Pediatrics in Review
Suggested Reading
Bindu PS, Taly AB, Kothari S, et al. Electro-clinical features and
magnetic resonance imaging correlates in Menkes disease. Brain
Dev. 2013;35(5):398405
Kaler SG. ATP7A-related copper transport diseases-emerging
concepts and future trends. Nat Rev Neurol. 2011;7(1):
1529
Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport
disorders: biochemical mechanisms, diagnosis, and treatment.
Curr Drug Metab. 2012;13(3):237250
Tang J, Donsante A, Desai V, Patronas N, Kaler SG. Clinical outcomes in
Menkes disease patients with a copper-responsive ATP7A
mutation, G727R. Mol Genet Metab. 2008;95(3):174181
Tmer Z. An overview and update of ATP7A mutations leading to
Menkes disease and occipital horn syndrome. Hum Mutat.
2013;34(3):417429
PRESENTATION
A 6-month-old white boy presents to the emergency department for pain on
manipulation of his right lower extremity. His father reports lifting him off the
couch the day before when the boys right leg had become stuck in a space
between the cushions. After his father pulled his leg free, the child appeared to be
uncomfortable, but his symptoms rapidly resolved. No other history of trauma is
reported. However, today the patient was seen crying when his older sister was
pulling on his right leg.
The patients perinatal history is unremarkable. The medical history is
signicant only for strabismus, which was recently noted by his pediatrician.
He is being formula fed and takes rice cereals and early-stage baby foods. He takes
no medications. Both height and weight are tracking at the 90th percentile. He is
meeting all developmental milestones.
On physical examination, the child is alert and interactive. His examination
ndings are notable for a blue hue to his sclerae that has been present since birth
(Figure 1). He has pain to palpation over the right anterior tibia and refuses to bear
weight on that leg. Skin examination reveals no ecchymoses, lacerations, marks,
or abrasions. He has no other areas of tenderness, and the remainder of his
physical examination ndings are normal. Intentional trauma is a concern given
the minimal force of the reported mechanism of injury that led to this childs
fracture. Radiographs in the emergency department reveal an oblique, nondisplaced, middiaphyseal right tibial fracture (Figure 2).
Genetics testing reveals the underlying diagnosis.
Figure 1. Recent photograph of the child at age 2 years. The blue hue to his sclerae has been
present since birth.
*Department of Pediatrics, Tripler Army Medical Center, Honolulu, HI.
Vol. 35 No. 11
NOVEMBER 2014
e57
DIFFERENTIAL DIAGNOSIS
Figure 2. Oblique, nondisplaced, middiaphyseal right tibial fracture.
DIAGNOSIS
Because of this patients blue sclerae and presentation with
a fracture, genetic testing is performed. COL1A1 and
COL1A2 sequencing analysis conrms a mutation
(c.3162delT) in COL1A1, the gene that encodes the a1-chain
of type 1 collagen. This child is diagnosed as having osteogenesis imperfecta (OI) type 1.
DISCUSSION
Nine subtypes of OI have been described. In type I OI, an
autosomal dominant mutation in the COL1A1 gene causes
premature termination of pro-a1-collagen messenger RNA
(mRNA). This abnormal mRNA is rapidly degraded by
nonsense mediated decay, and as a result, patients with
type I OI have only 50% of the normal procollagen mRNA,
generated from the unaffected allele. As a result of this
decreased production of type 1 collagen, patients with type I
OI have increased bone fragility and an increased rate of
fractures. Patients with type I OI can have slightly short
stature and blue sclerae. They commonly have vertebral
fractures but usually have an absence of major bone deformities. Hearing loss can develop, usually after age 10
years. Dentogenesis imperfecta is typically absent in type I
OI, but kyphosis and scoliosis may develop over time.
e58
Pediatrics in Review
MANAGEMENT
Treatment of OI involves a coordinated multidisciplinary
approach that consists of physical and occupational therapy,
orthopedic surgical interventions, and medications to reduce
fracture rates, prevent long-bone deformities and scoliosis,
PROGNOSIS
The prognosis for an individual with OI varies greatly,
depending on the number and severity of symptoms. Patients with type I (mild type) typically experience most of
their fractures before puberty. It is uncommon to have bone
deformities, and they are usually of normal or near-normal
stature. Hearing loss is a major concern.
PATIENT COURSE
This child had 4 additional fractures in his feet and legs
during the next 2 years. He was then referred to the pediatric
endocrinology department at age 2 years. A bone density
scan revealed reduced bone mineral density of the lumbar
spine (z score 2.0) (Figure 3). His 25-hydroxyvitamin D
level was 20 ng/mL (50 nmol/L) (borderline for vitamin
D deciency), and treatment was initiated with vitamin D
(ergocalciferol) at 2000 IU/d. His 25-hydroxyvitamin D
level normalized to 35 ng/mL (87 nmol/L) within 2 months.
In addition, intravenous pamidronate treatment was initiated for 3 days every 3 months, and consideration is currently being given to placing intramedullary telescoping
rods in both lower extremities.
Figure 3. Bone mineral density of the lumbar spine was 0.361 g/cm2 at
age 2 years, demonstrating moderate osteopenia (z score 2.0).
Vol. 35 No. 11
NOVEMBER 2014
e59
Summary
Pediatricians play an important role in diagnosing OI as a cause of
fracture and may be asked to differentiate this uncommon
genetic diagnosis from intentional trauma and other causes of
fracture.
Early referral to a pediatric endocrinologist, physical therapist,
and orthopedic surgeon for the evaluation and treatment of low
bone mass and recurrent fractures is important because early
medical and surgical intervention may help to minimize the rate
of future fractures, even within the rst year of life.
Continued follow-up with physical and occupational therapy,
audiology testing, and regular evaluations of dental health are all
essential for children with OI.
e60
Pediatrics in Review
Suggested Reading
Rauch F, Glorieux FH. Osteogenesis imperfecta, current and future
medical treatment. Am J Med Genet C Semin Med Genet. 2005;139C
(1):3137
Ruck J, Dahan-Oliel N, Montpetit K, Rauch F, Fassier F. Fassier-Duval
femoral rodding in children with osteogenesis imperfecta receiving
bisphosphonates: functional outcomes at one year. J Child Orthop.
2011;5(3):217224
van Dijk FS, Cobben JM, Kariminejad A, et al. Osteogenesis
imperfecta: a review with clinical examples. Mol Syndromol.
2011;2(1):120
2015
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aeruginosa, and other gram-negative organisms. Antibiotic treatment should again be directed at the most common pathogens
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The risk of VAT peaks at approximately 4 days after intubation, with an estimated incidence of 2% to 11%. The onset of
bacterial tracheitis in children with long-standing tracheotomies
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In general, tracheotomy-associated tracheitis is not aggressive
and, if there is close follow-up, can be treated in the outpatient setting with oral antibiotics, topical ciprooxacin and
dexamethasone, or tobramycin and dexamethasone drops
directed into the tracheotomy for several days. Recurrence
of tracheitis is more common in children with a long-term
tracheotomy.
During the past several decades, the incidence, diagnosis, and management of bacterial tracheitis have been
inuenced by new vaccines and by the heightened awareness among physicians of the alarmingly high morbidity
associated with delayed recognition. Despite its low incidence, clinicians must consider the possibility of bacterial
tracheitis in any patient with acute respiratory decompensation
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