Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_37_библиотеки_им_акад_М_И_Перельмана
.pdf
CHAPTER 9 Diagnostic Imaging in the Neonate
https://t.me/medicina_free
219
A
FIGURE 9.11 Axial T2-weighted image through the posterior fossa (A) demonstrates the high-signal cerebrospinal fluid in the posterior
fossa cyst, which communicates with the fourth ventricle more anteriorly (open arrow). Midsagittal T1-weighted image (B) demonstrates
a Dandy-Walker variant in this patient. The partial formation of the vermis seen best on the sagittal image defines a Dandy-Walker variant
(black arrow).
whereas in T2-weighted imaging, fluid is white.
Most pathologic conditions are characterized
either by the distortion of the normal anatomy
or by edema, which is manifested as increased
fluid in an otherwise normal structure or within
the particular lesion. Therefore, if one looks for a
fluid collection (e.g., CSF in the ventricles of the
brain, such as CSF in the subdural space around the
cord; orbital fluid of the aqueous humor; or fluid in
the heart or urinary bladder), one usually can determine whether the imaging sequence is T1 weighted,
in which the fluid appears black, or T2 weighted,
in which the fluid appears white. On T1-weighted
sequences, a pathologic condition is seen as a black
or lower signal because a pathologic state is associated with increased water in the area of abnormality.
In T2-weighted sequences, the pathologic lesion
tends to be white.
Focused Discussion: Fetal MRI
Historically, US has been the most effective and
informative imaging modality in fetal medicine.
However, as the field of maternal-fetal medicine
B
evolves, fetal MRI is becoming an essential part
of the imaging armamentarium (Fig. 9.12). The
explosion in fetal MRI is the result of advanced
instrumentation, imaging sequence development,
and expertise in interpretation. The newer equipment and modified sequences shorten acquisition
time and therefore minimize artifact, yielding better-quality images.
US continues to offer the advantage of availability, portability, and real-time acquisition.
MRI, like US, is performed without ionizing
radiation. Although fetal US continues to be the
screening modality of choice, MRI as an additional
modality can clarify US findings. Literature also
has demonstrated that fetal MRI can identify
additional abnormalities not seen by fetal US,
particularly in the central nervous and genitourinary systems. A fetal MRI examination takes
much longer to perform than an US study, and
in general, the imaging is not real-time. However,
MRI offers a number of advantages. Tissue
characterization with MRI is superior to that
of US. This is particularly helpful when evaluat-
ing the fetus for developmental anomalies of the
UNIT TWO Support of the Neonate220
FL
https://t.me/medicina_free
FIGURE 9.12 Sagittal T2-weighted fetal magnetic resonance imaging
demonstrates a defect within the lumbosacral spine with associated cystic structure consistent with a lumbosacral myelomeningocele. The associated findings
of a small posterior image with dilatation of the lateral ventricles, consistent with
a Chiari II malformation, are also partially visible.
central nervous system. Cerebral sulcation, cortical
and white-matter development, and ventricular size
and configuration can be readily displayed with
fetal MRI. MRI can clarify spinal abnormalities
suggested by screening US. MRI is an essential
part of the Management of Myelomeningocele
Study (MOMS Trial) comparing the results of prenatal versus postnatal repair of myelomeningocele.
Another important role of fetal MRI relates to
imaging of the airway and lungs. Valuable infor-
mation concerning the degree, location, and nature
of bronchial obstruction can have a significant effect
on ex utero intrapartum treatment (EXIT) procedures to deal with complex anatomy that could
result in fatal airway compromise after birth.
NUCLEAR SCINTIGRAPHY
Nuclear scintigraphy is the most physiologic of
the tools commonly used in neonatal imaging. A
pharmaceutical is tagged with a radiotracer, which
is a radioactive isotope that can be detected by a
nuclear medicine camera. The pharmaceutical may
be injected intravenously, given orally, or delivered
directly into the urinary bladder. The pharmaceutical is distributed in the body based on the parent
compound to which the radioisotope is chelated or
bound. The patient then is imaged using a detector
that maps the distribution of the tagged isotope in
the body.
The radiation dose in scintigraphy is small.
With the doses used for diagnostic purposes, there
is little risk to the individual and no risk to anyone who is in immediate contact with the patient.
The pharmaceutical agents have both a biologic
half-life related to the natural elimination of the
parent compound from the body and a radioactive
half-life determined by the isotope used to label
the pharmaceutical. The spatial resolution is poor,
but the contrast resolution is exquisite because the
radiopharmaceutical is distributed so specifically
within the body.
Clinical Utility in the Neonatal
Intensive Care Setting
Three common investigations for which nuclear
medicine is well suited are renal scintigraphy,
hepatobiliary imaging, and splenic imaging. In
patients with the syndrome defined by vertebral,
anal, cardiac, tracheal, esophageal, renal, and limb
(VACTERL) anomalies, renal scans can be helpful
in determining the number and location of the
kidneys. Renal scintigraphy can be used to quantify
relative renal function. Scintigraphy is a functional
way to evaluate the degree of obstruction in
hydronephrosis. Nuclear cystography has a very
low radiation dose; therefore, it is a good method
for following vesicoureteral reflux. Fluoroscopic
cystography usually is performed for the initial evaluation because the excellent spatial resolution can
assist in defining anatomic abnormalities that may
be responsible for reflux (e.g., that might be missed
with the poor spatial resolution of nuclear imaging).
Hepatobiliary imaging can assist in the evalu-
ation of the jaundiced patient. The radiopharma-
ceutical is extracted from the blood pool by the liver
and excreted like bile, allowing one to determine
transit time and flow of the bile from the liver into
the gallbladder, through the common bile duct, and
into the duodenum. Hepatobiliary imaging can
help distinguish neonatal hepatitis from biliary
atresia. In neonatal hepatitis, there is limited
clearance of the pharmaceutical agent from the
blood by the liver; therefore, the liver shows little
activity compared with the background, but a small
amount of activity is excreted into the bowel. In
biliary atresia, the clearance or extraction of
https://t.me/medicina_free
the radiopharmaceutical agent from the blood is
closer to normal, but the isotope never leaves
the liver, and therefore no activity is seen in the
duodenum and small bowel, even on delayed
images. A choledochal cyst accumulates radiotracer
and is diagnosed by an intense area of focal activity
and a dilated biliary system more proximally.
Splenic imaging can be performed with technetium sulfur colloid, which is taken up in the Kupffer
cells in the liver and spleen. Alternatively, radiolabeling of red blood cells can be used for splenic images
because damaged cells are sequestered in the spleen.
Splenic imaging frequently is helpful in patients
with complex congenital heart disease and situs
abnormalities to diagnose asplenia or polysplenia.
CHAPTER 9 Diagnostic Imaging in the Neonate
221
Focused Discussion: Renal
Scintigraphy
The radiopharmaceutical choices for renal imag-
ing are either cortical agents that bind in the renal
cortex, filtered agents that transit the cortex and
then are excreted into the collecting system, or a
combination of both cortical and filtered agents.
Cortical agents are useful in defining the size,
number, location, and relative function of the
kidneys (when there are two kidneys). The US
characteristics of multicystic dysplastic kidney
(MDK) usually are diagnostic; however, renal
scintigraphy (Fig. 9.13) occasionally can help dif-
ferentiate the hydronephrotic form of MDK from
severe ureteropelvic junction (UPJ) obstruction.
A combination agent, such as mercaptoacetyltriglycine (MAG3), is useful in the evaluation of
hydronephrosis because one can determine the
relative function of each kidney and evaluate the
degree of obstruction. Addition of the furosemide
(Lasix) washout study augments the evaluation
of hydronephrosis by rendering a washout curve
that is indicative of the severity of obstruction.
In evaluating hydronephrosis, it is generally helpful to place a catheter in the urinary bladder to
prevent possible vesicoureteral reflux from confounding the examination results. Although all
of these tests can be performed in the newborn
period, the concentrating ability of the newborn
kidney is marginal. Therefore, the tests often are
reserved until the patient is 3 to 6 months of
age to improve their accuracy and prognostic
capability.
Min
FIGURE 9.13 This posterior image from a diethylenetriaminepentaacetic
acid (DTPA) renal scan demonstrates the collecting system, ureter, and urinary
bladder associated with the functioning right kidney (black arrow). The multicystic dysplastic kidney on the left shows no functional renal tissue (open arrow).
3
POSITRON EMISSION
TOMOGRAPHY
Background
Clinical utilization of positron emission tomography (PET) in neonates and young infants
has been limited because the radiation dose is
significant. Nonetheless, the recent growth of and
interest in PET for specialized applications argue for
its understanding.
The concept of PET was initially proposed in the
early 1950s, and medical PET was first attempted in
the mid-1970s. The physics of PET involves the introduction of a positron-emitting radiopharmaceutical
combined with a biologically active substance. These
short–half-life radiopharmaceuticals require a cyclotron to produce and are therefore less available than
the pharmaceuticals most commonly used in routine
nuclear scintigraphy. A positron is a particle with the
opposite charge of an electron that travels only a very
short distance within the body until it hits an electron.
The collision of the positron with an electron results in
two annihilation electrons (gamma rays) of the specific
energy 511 keV being emitted in opposite directions
at equal velocity. The location in space of the point
source of the electrons can be calculated from the
UNIT TWO Support of the Neonate222
https://t.me/medicina_free
fractional difference in the time it takes for the electron
to reach the detector. The positron-emitting tracer
attached to a metabolically active substance is introduced into the body intravenously, and the radiotracer
is distributed throughout the body with the active
metabolite. After 30 to 60 minutes of redistribution
within the body, a scintillation scanning device detects
the nearly coincident paired gamma rays. In the body,
bones and other attenuators block some of the electrons from reaching the detector. Therefore, a means of
identifying the blockers is needed.
CT happens to be a very efficient means of
locating bones and other blockers but has the added
benefit of rendering anatomic images. This allows for
more precise localization of signal and its relationship
to internal structures. Because of the ability to acquire
both anatomic and metabolic information simultaneously, the combination of PET and CT (PET/CT)
has been responsible for the rapid growth of PET in
recent years. Not only can one identify regions of
high metabolic activity, but also the location can be
more precisely correlated with the internal anatomy,
with significant improvement in diagnostic accuracy.
In humans, the most common pharmaceutical used
is fluorodeoxyglucose (FDG), which is a glucose
analog. FDG is distributed like glucose throughout
the body. Regions of abnormal metabolic activity
can be identified and, with CT, localized to a specific
structure in the body. A metabolically active tumor,
for instance, would demonstrate a focus of increased
activity in a PET image. For example, if it were
localized in the anterior mediastinum, it would be
consistent with the diagnosis of lymphoma.
Clinical Utility in the Neonatal
Intensive Care Setting
The relatively high radiation dose associated with PET
has limited its use, but it has been effectively utilized
in staging neonatal neoplasm. The role PET will play
in the evaluation of hypoxic-ischemic injury and the
evaluation of neonatal seizures is yet to be determined.
INTERVENTIONAL RADIOLOGY
Intervention is one of the newest but most
rapidly growing subspecialty areas in medical
imaging. Interventional radiology has assumed
an important role as a minimally invasive way to
treat disease. Imaging can also direct the surgical
approach. From a practical standpoint, there are
four major areas of radiology intervention: (1)
vascular access; (2) tissue sampling for minimally
invasive diagnosis of neoplasm or infection; (3)
catheter or needle drainage of fluid collections
or abscesses; and (4) directed delivery of cells,
chemotherapy, or embolic material, which may
be used to diminish flow to a vascular lesion.
Any of the imaging modalities may be used to
guide the intervention, but the most commonly
used are fluoroscopy, ultrasound, and CT.
Clinical Utility in the Neonatal
Intensive Care Setting
Vascular access is the most commonly requested
radiologic intervention in most pediatric institutions. Ultrasound or fluoroscopy can be used to
visualize veins for venous access. Although bed-
side catheter placement with confirmation of placement by ultrasound or radiography is often possible,
placement in interventional radiology is sometimes
necessary in difficult cases, such as patients with
aberrant anatomy, vascular narrowing, or occlusion.
Tissue sampling is often performed to diag-
nose neoplasm. In general, utilizing ultrasound,
fluoroscopy, or CT, a needle is placed into an area
of abnormal tissue to obtain either a fine-needle
aspirate or, often in solid tumors, a core needle
biopsy. The advantage of a core needle biopsy is
that the tissue obtained is frequently large enough
to complete many of the pathologic studies necessary in the pretreatment evaluation of the neoplasm.
This can be particularly helpful in patients in whom
a neoplasm, once defined, can be pretreated before
definitive surgical resection is performed.
Cysts or abscesses can be drained, obviating the
need for an open surgical procedure and thus minimizing morbidity and shortening recovery time.
A gastrostomy or gastrojejunostomy tube also
can be placed in a minimally invasive manner,
rather than a more invasive surgical procedure.
This can be an ideal approach for the placement of
a temporary feeding tube.
Directed delivery of chemotherapy has been used
in neonatal units for the treatment of hepatoblastoma. Chemotherapy can be directed through
the hepatic artery into the involved lobe and the
tumor reduced in size before excision. By reducing
the size of the tumor preoperatively, a previously
nonresectable tumor can sometimes be removed.
CHAPTER 9 Diagnostic Imaging in the Neonate
https://t.me/medicina_free
223
Another example of directed delivery is the
embolization of infantile hepatic hemangioma.
Infantile hepatic hemangioma is a rare cause of congestive heart failure resulting from an extracardiac
shunt in the neonatal period. It is possible to embolize
the benign neoplasm, thereby diminishing the shunt
and correcting the heart’s failure. Vein of Galen malformation is another extracardiac vascular shunt that
frequently predisposes the patient to high-flow cardiac
failure. A spectrum of vein of Galen malformations
exists, and the success of embolization is highly dependent on the degree of vascular insufficiency resulting
from the steal associated with a high-flow lesion. In
patients who present early and in florid heart failure,
the outcomes are predictably worse than in patients
who present later with an abnormality discovered
during a routine physical examination, in which an
intracranial bruit might be identified.
Finally, directed delivery for cell implanta-
tion and genetic engineering shows great promise.
These areas are early in their development, but the
ability to direct a catheter to a specific organ for cell
implantation or gene therapy will clearly have a role
in future applications of interventional radiology.
Focused Discussion: Vascular Access
The availability of ultrasonographic equipment
can allow placement of PICCs or central venous
catheters in vessels as small as 2 mm. With US
imaging, the vessel is visualized directly. Fluoroscopic
guidance requires limited venography by injecting
contrast through a peripheral IV line. After visualization with either ultrasonography or fluoroscopy,
a 21-gauge needle is placed into the selected vessel.
Once good blood return confirms the intraluminal position of the needle tip, a 0.18-wire is passed
through the needle. The needle is removed, and the
tract is dilated. Next, a peel-away sheath is placed
over the wire. The catheter is sized and then passed
through the peel-away sheath. The location of the
catheter tip is confirmed fluoroscopically.
PICTURE ARCHIVING AND
COMMUNICATION SYSTEMS
The widespread use of picture archiving and com-
munication systems (PACSs) has had a significant
effect on diagnostic imaging and medicine throughout the United States and the world. Simply put, a
BOX
9.3
• Acquires,displays,distributes,andarchivespatientimages
• Displaysdigitalimagesoncomputermonitors(softcopy)
• Enablesmanipulationofimagestoenhancevisualization
• Providesbrightness,contrast,magnication
• Makessimultaneousviewingatmultiplesitespossible
• Improvesefciencyandacceleratesresultsreporting
• Enhancesdecisionsupport,whichimprovespatientmanagement
PACS is the process of image display, distribution,
and archive as it relates to radiology (Box 9.3).
PACS allows images obtained by CT, MRI,
ultrasound, nuclear imaging, and plain radiography to be distributed to any location for simultaneous access by any number of caregivers and
specialists. Images can be distributed via a local
network within a hospital, over a regional network
to a group of providers, or over the Internet for
viewing anywhere in the world. Systems have been
developed that offer resources never before possible
with film. Archives are protected for patient privacy
and safety.
For a number of years, CT, MRI, and US images
have been acquired digitally or, at a minimum, were
handled digitally after an analog-to-digital conversion. Before computerized radiography (CR) and
digital radiography (DR), x-ray images obtained
on film could be converted into a digital format by
scanning the film in a laser scanner. Fluoroscopic
and x-ray images are now captured digitally with
CR or DR and thereby become immediately available for soft-copy reading from a computer monitor
as opposed to viewing a radiograph on film at a
view box, known as hard-copy reading. CR is very
similar to conventional radiography except that it
replaces film with a phosphorescent imaging plate
that transfers the latent image into a digital format
when developed. DR provides for direct conversion
of the x-ray into an electronic digital format that
requires no processing of the imaging plate.
The flexibility provided by digital imaging permits extensive manipulation of images. The contrast
and brightness (window and level) can be adjusted
to optimize visualization of selected images or
even portions of an image. These parameters can
be changed when viewing an image to enhance
a particular structure or finding. The window and
PICTURE ARCHIVING AND
COMMUNICATION SYSTEM
UNIT TWO Support of the Neonate224
https://t.me/medicina_free
level can be changed when viewing a chest x-ray
image, for example, to accentuate the lung, bones,
a central catheter, an endotracheal tube, or a gastrostomy button. Images can be magnified, rotated,
inverted (black to white and white to black), and
even screened by sophisticated computer programs
to improve the detection of pathology. Radiology
reports can be transcribed with voice-recognition software, allowing the radiologist to edit and
sign a report within minutes of acquisition. The
reports then are associated with images from the
examination. It is now common to have images
and interpretations available on a computer
monitor in the NICU by the time the patient
returns from radiology. Reports and images then
are assimilated into the patient’s electronic medical record. PACS is a powerful tool that improves
medical management by translating bits of data into
clinically relevant information. It enhances medical
care and decision support by making images and
interpretations available simultaneously in numerous locations, including in the NICU and often
at the bedside, in a fraction of the time previously
necessary.
FAMILY EDUCATION AND
INVOLVEMENT
The NICU team can have a positive effect on
imaging by helping educate the parent. When
parents understand a procedure and know what to
expect, they can be very helpful. Not only is the
quality of the imaging better, but also the experience
of the parent and patient is improved. An informed
parent can effectively assist in the imaging process when included in the treatment plan.
An optimal study requires motion-free imaging.
Even with fluoroscopy and ultrasonography in
which motion is recorded, the actual acquisition of
the image must be free of extraneous motion. With
x-ray and CT studies, shortening the acquisition
time helps to accomplish this. Respiratory motion
can be limited by taking the image at the end of
inspiration. Some modalities cannot acquire the
image data fast enough to eliminate motion. These
examinations frequently require sedation. The most
common modalities to require sedation are
MRI, nuclear scintigraphy, and CT.
Sedation protocols vary from institution to insti-
tution, but certain aspects of sedation are universal.
The patient must be given nothing by mouth
(NPO) for a period of time before sedation. It
is simply unsafe to sedate a patient who has eaten
recently. Failure to keep a patient NPO is one of
the most common reasons that a scheduled examination has to be canceled and rescheduled. Parents
generally are informed of the need for sedation
and asked for consent (verbal or written). The
choice of sedation depends on many factors. These
include the length of the examination, the fragility
of the patient, and the experience and training of
the individual responsible for sedation. The route of
administration also is variable and includes IV, intramuscular (IM), oral (PO), rectal, and inhalation. The
sedated patient is monitored throughout the
procedure and recovery. Recovery can occur in
the imaging suite, a recovery area, or newborn
center, but the patient must be monitored until
fully recovered.
Some unique aspects of newborn care require
special attention in the imaging suite that might
not be as important in older patients. These
important issues are of even more concern in
the sedated patient. Thermoregulation is always of
concern in the neonate. Imaging suites frequently
are cold. Maintaining body heat is especially
problematic in studies that require prolonged
imaging times and in those in which the patient
could get wet, such as cystography and fluoroscopic GI procedures. Blankets and overhead
warmers can mitigate the problem, but providers must anticipate the issue.
Fluid administration also can be problematic in
the neonate. Newborns need dextrose in their IV
lines, especially if they are not feeding. Therefore,
it is important in these patients to keep IV lines
open and functioning. Most IV pumps are not
compatible with MRI, and many cause interference that degrades image quality. However, it is
not appropriate to suspend fluid administration
for the duration of the study. The issue should be
anticipated and addressed in a timely fashion.
Care of a critical newborn in the imaging
suite can be challenging. It requires cooperation
between the NICU staff (nursing and medical) and the imaging staff. Parental education
enables the parents to participate in the care of
CHAPTER 9 Diagnostic Imaging in the Neonate
https://t.me/medicina_free
225
their newborn and has a positive effect on the
newborn’s imaging experience.
Numerous imaging alternatives are available for
the evaluation of any patient condition. The best
imaging choice varies depending on local expertise
and availability. A clear understanding of the clinical
question, patient condition and comorbidities, and
the differential diagnosis being considered is essential for optimal imaging and interpretation. The
clinician should consider the pros and cons of
each modality and consult with a radiologist if
there is any uncertainty as to the best method
of imaging.
REFERENCES
1. American College of Radiology. SPR Practice Parameter for
Imaging Pregnant or Potentially Pregnant Adolescents and Women with
Ionizing Radiation. Resolution 39. Revised 2018. https://www.acr.
org/-/media/ACR/Files/Practice-Parameters/Pregnant-Pts.pdf.
Accessed January 5, 2019.
2. Ares G, Hunter CJ. Central venous access in children: indica-
tions, devices and risks. Curr Opin Pediatr. 2017;29(3):340.
3. Barkovich AJ, Raybaud C. Pediatric Neuroimaging. 6th ed.
Philadelphia: Lippincott Williams & Wilkins; 2018.
4. Barrington SF. Atlas of Clinical Positron Emission Tomography, with
Interactive DVD. 2nd ed. Abingdon, OX: CRC Press; 2005.
5. Brenner DJ, Elliston CD. Estimated radiation risks potentially
associated with full-body CT screening. Radiology. 2004;232(3):735.
6. Brenner D, Elliston CD, Hall EJ, Berdon W. Estimated risks
of radiation-induced fatal cancer from pediatric CT. AJR Am J
Roentgenol. 2001;176(2):289.
7. Browne LP. What is the optimal imaging for vascular rings and
slings? Pediatr Radiol. 2009;39(2):S191.
8. Coley BD. Caffey’s Pediatric X-Ray Diagnosis: An Integrated
Imaging Approach. 13th ed. Philadelphia, PA: Elsevier; 2018.
9. Donnelly LF. Fundamentals of Pediatric Imaging (Fundamentals of
Radiology). 2nd ed. Philadelphia, PA: Elsevier; 2016.
10. Engel C, Silva C, Baker K, Goodman TR. Underutilized ultra-
sound applications in the neonatal intensive care unit. Ultrasound
Q. 2012;28(4):299.
11. Epelman M, Kreiger PA, Servaes S, Victoria T, Hellinger JC.
Current imaging of prenatally diagnosed congenital lung lesions.
Semin Ultrasound CT MRI. 2010;31(2):141.
12. Fleming SE, Kim JH. Ultrasound-guided umbilical catheter
insertion in neonates. J Perinatol. 2011;31(5):344.
13. Hall EJ, Brenner DJ. Cancer risks from diagnostic radiology. Br J
Radiol. 2008;81(965):362.
14. Hanneman K, Newman B, Chan F. Congenital variants and
anomalies of the aortic arch. Radiographics. 2017;37(1):32.
15. Hellinger JC, Pena A, Poon M, Chan FP, Epelman N. Pediatric
computed tomographic angiography: imaging the cardiovascular
system gently. Radiol Clin North Am. 2010;48(2):439.
16. Jain A, McNamara PJ, Ng E, El-Khuffash K. The use of targeted
neonatal echocardiography to confirm placement of peripherally inserted central catheters in neonates. Am J Perinatol.
2012;29(2):101.
17. Johnson KN, Thomas T, Grove J, Jarboe MD. Insertion of
peripherally inserted central catheters in neonates less than 1.5
kg using ultrasound guidance. Pediatr Surg Int. 2016;32(11):1053.
18. Karber BC, Nielsen JC, Balsam D, Messina C, Davidson D.
Optimal radiologic position of an umbilical venous catheter tip
as determined by echocardiography in very low birth weight
newborns. J Neonatal Perinatal Med. 2017;10(1):55.
19. Katheria AC, Fleming SE, Kim JH. A randomized controlled
trial of ultrasound-guided peripherally inserted central catheters
compared with standard radiograph in neonates. J Perinatol.
2013;33(10):791.
20. Kunisaki SM, Fauza DO, Nemes LP, et al. Bronchial atresia: the
hidden pathology within a spectrum of prenatally diagnosed
lung masses. J Pediatr Surg. 2006;41(1):61.
21. Lachman RS. Taybi and Lachman’s Radiology of Syndromes,
Metabolic Disorders and Skeletal Dysplasias. 5th ed. St Louis:
Mosby; 2006.
22. Lai WW, Mertens LL, Cohen MS, Geva T, eds. Echocardiography
in Pediatric and Congenital Heart Disease. 2nd ed. New Jersey:
Wiley-Blackwell; 2016.
23. McNamara PJ, Ng E, El-Khuffash K. The use of targeted
neonatal echocardiography to confirm placement of peripherally inserted central catheters in neonates. Am J Perinatol.
2012;29(2):101.
24. Nguyen J. Ultrasonography for central catheter placement in the
neonatal intensive care unit—a review of utility and practicality.
Am J Perinatol. 2016;33(6):525.
25. Osborn AG, Hedlund GL, Salzman KL. Osborn’s Brain: Imaging,
Pathology and Anatomy. 2nd ed. Philadelphia, PA: Elsevier; 2017.
26. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from
CT scans in childhood and subsequent risk of leukaemia and brain
tumours: a retrospective cohort study. Lancet. 2012;380(9840):499.
27. Rumack CM, Levine D. Diagnostic Ultrasound. 5th ed. St Louis:
Elsevier; 2017.
28. Sharma D, Farahbakhsh N, Tabatabii SA. Role of ultrasound for
central catheter tip localization in neonates: a review of the current
evidence. J Matern Fetal Neonatal Med. 2019;32(14):2429. https://
doi.org/10.1080/14767058.2018.1437135. Epub ahead of print.
29. Siegel M. Pediatric Sonography. 5th ed. Philadelphia: Lippincott
Williams & Wilkins; 2018.
30. Spranger JW, Brill PW, Hall C, Nishimura G, Superti-Furga
A. Bone Dysplasias: An Atlas of Genetic Disorders of Skeletal
Development. 4th ed. New York: Oxford University Press; 2018.
31. Stark D, Bradley Jr W, Bradley WG. Magnetic Resonance Imaging.
3rd ed. St Louis: Mosby; 1999.
32. Swaiman KF, Ashwal S, Ferriero DM, Schor NF. Pediatric
Neurology: Principles and Practice. 6th ed. St Louis: Elsevier; 2017.
33. Townsend SF, Rumack CM, Thilo EH, Merenstein GB,
Rosenberg AA. Late neurosonographic screening is important
to the diagnosis of periventricular leukomalacia and ventricular
enlargement in premature infants. Pediatr Radiol. 1999;29(5):347.
34. Volpe JJ, Inder TE, Darras BT, et al. Neurology of the Newborn. 6th
ed. Philadelphia: Elsevier; 2017.
PHARMACOLOGY IN
https://t.me/medicina_free
10
ptimal pharmacotherapy involves dosing drugs to deliver the maximum
O
minimum toxicities. Determining the optimal
pharmacotherapy for neonates is problematic in
that much of the data have been extrapolated from
research in adults, children, and laboratory animals.
Neonates show significant differences in processing and responding to drugs compared with
older children and adults.
variability in the response to pharmacotherapies
among neonates. Gestational age, chronologic
age, and disease state alter a neonate’s ability to
metabolize medications and affect the response
to the drug.
illustrating how rational decisions can be made for
pharmacotherapies used in neonatal intensive care
unit (NICU) patients. The chapter also includes
discussions on strategies to avoid medication errors,
strategies for drug delivery, information on how
therapeutic hypothermia affects pharmacokinetics,
and a summary of recent pharmacokinetic studies
in NICU patients.
intended beneficial effects with the
This chapter discusses neonatal pharmacology,
NEONATAL CARE
LAWRENCE C. KU, CHI HORNIK, AND DEANNE BUSCHBACH
39,46
There is also great
46,72
PHYSIOLOGY
Pharmacodynamics and
Pharmacokinetics
The drug-receptor theory states that the amount
and duration of exposure of a drug to a receptor determine its effectiveness. Pharmacokinetics
describes what the body does to the drug
(exposure over time), which then determines
how a drug is available to the receptors and for what
length of time (Fig. 10.1).
describes what the drug (or its active metabolite, such as caffeine for theophylline or
morphine-3 and morphine-6 glucuronide for
morphine) does to the body at certain concentrations (effect over exposure). The drug’s
effectiveness also depends on receptor availability,
the affinity of the drug for the receptor, and cellular functions in response to the drug–receptor
interaction.
Antagonist drugs block a receptor’s cellu-
lar and physiologic activity (e.g., naloxone),
whereas agonist drugs elicit the receptor’s action
(e.g., cardiovascular agents such as dopamine
and epinephrine). Some drugs act with recep-
tors to increase or decrease gene expression (e.g.,
antenatal steroids such as betamethasone), whereas
others affect cell membrane permeability. Some
drugs, such as methylxanthines, increase or decrease
the amount or activity of second-messenger molecules within cells. Antibiotics and antiviral agents
act through some of these mechanisms to reduce
the viability of pathogenic organisms by changing
vital characteristics and functions. Readers should
note that most drugs have more than one effect, so
although the desired therapeutic effect may occur,
the drug’s other effects can limit its usefulness. Side
effects, which can vary from minor to prohibitive,
occur within the therapeutic range of concentration. Toxic effects result from a drug overdose
or serum concentrations higher than the recommended therapeutic range.
Individual infants may have idiosyncratic responses
to medications, which are rare and unpredictable
reactions, as well as expected responses. Different,
37,78
Pharmacodynamics
BLUE type highlights content that is particularly applicable to clinical settings.
226
CHAPTER 10 Pharmacology in Neonatal Care
CC
Pharmacokinetics Pharmacodynamics
https://t.me/medicina_free
227
Dose–response
Dose –
FIGURE 10.1 Variability in dose–response relationship can be the result
of differences in pharmacokinetics or pharmacodynamics. C, Drug concentration
(plasma or serum).
– response
competing mechanisms related to postmenstrual
age (PMA) in weeks, postnatal age (PNA) in days,
disease, genetics, and drug interactions can lead to
infants who exhibit a drug response less than that
expected for a usual dose and other infants who
exceed the expected response for a given dose and
drug level. Unpredictable adverse reactions differ
from expected responses. Patients may become tolerant to a given drug dosage, as is commonly seen
with opioids. Tachyphylaxis, a rapid decrease in
drug response without a dosage change, may be
related to limited receptors or other intracellular
mechanisms.
14,33
Developmental differences related to infant
physiology are responsible for significantly different pharmacokinetics in infants compared
with adults and older children. Characteristics
affecting drug disposition in infants include total
serum protein available for binding to drugs, body
water composition, kidney function, and skin thickness affecting the intradermal absorption of drugs;
these characteristics change drastically over a period
of days, weeks, and months after birth.
16,40,85
Many enzymes responsible for the metabolism of
drugs prescribed to infants also undergo significant changes in levels of expression and activity
with age.13 In many cases, these enzymes will have
significantly reduced activity at birth that slowly
increases with postnatal age. As a result, drugs that
are predominantly metabolized by these enzymes
will demonstrate different rates of elimination
among infants of different ages.
Developmental differences in the number
and function of receptors and intracellular
mechanisms are also critical to estimating
drug actions.77 For example, neonates may have
increased sensitivity to morphine compared with
adults due to higher levels of expression of the mu
opioid receptor in neonates.54 Changes in alpha-
and beta-adrenergic receptors also occur with
gestational and chronologic age and must be
considered in determining dosages with vasopressors and inotropes.
8
A clinician determines a drug regimen and
dosage largely on the likelihood of achieving
the desired therapeutic response with minimal
toxic effects in the “average” patient. In concept, the clinician does this by targeting a drug
concentration in the body compartment where
the desired effect is wanted.
Plasma concentration is often used as a surrogate for
effect when the relationship between concentration
(C) and effect has been demonstrated in similar
patients. The minimum effective concentration (MEC)
is the concentration at which 50% of patients
exhibit the desired response (Table 10.1). The
maximum safe concentration (MSC) is that at
which 50% of patients exhibit a toxic response
(Fig. 10.2). The therapeutic index is calculated as the
ratio of MEC to MSC. Drugs with a narrow ther-
apeutic index (i.e., where the MEC is close to
the MSC) will require careful considerations
during patient care, such as drug-level assessments or close monitoring for signs of toxicities.
To elicit the desired therapeutic effect, the drug
must be delivered to the receptor and remain
available for an appropriate amount of time.88 If a
clinician aims to continue the therapy beyond a
single dose, then plasma concentration at steady
state (Css) is targeted within the MEC and the
MSC, where most patients exhibit the desired
effect and few suffer toxic effects. With ideal
maintenance therapy, the drug administered
should equal the drug elimination. The timedependent variability around the Css depends
on the dose, dosage interval, and drug disposition. Even before clinicians consider the
age-related changes in drug metabolism when
prescribing maintenance therapy for neonates,
UNIT TWO Support of the Neonate228
Therapeutic range
Response (%)
Drug concentration
https://t.me/medicina_free
TABLE
10.1
ABBREVIATION ABBREVIATION
C
Css
MEC
MSC
F
Vd
Cl
t
½
L, Liter = 1000 milliliters; mg, milligram = 1000 micrograms.
ABBREVIATIONS
DEFINED
Drug concentration
(plasma or serum)
Steady-state concentration (average)
Minimum effective
concentration
Maximum safe
concentration
Extent of drug availability (0-1): how much
active drug gets to the
systemic circulation
Volume of distribution:
relates to loading dose
Clearance: relates to
maintenance dose
Drug elimination halflife: relates to the time
course of changes in
drug concentration
UNIT OF
MEASUREMENT
mg/L
mg/L
mg/L
mg/L
Unitless
L/kg
L/kg/h
Hours
clinicians should anticipate the need to adjust
dosages regularly for changes in infant body
weight and composition. There is a 10-fold
variation in weight range among NICU patients
(0.5 to 5 kg). For term newborns, the weight is
expected to double in the first 3 to 4 postnatal
months, whereas in premature infants, the rate
of weight gain can be more rapid.
87
The target Css is influenced by the amount of
drug bound to plasma protein. It is only the free,
unbound drug that exerts its effect on receptors and
is subject to elimination in the body. In a newborn,
unconjugated bilirubin can displace numerous
drugs of lower protein affinity, including ampi-
cillin, penicillin, phenobarbital, and phenytoin,80
whereas other drugs can displace unconjugated
bilirubin, which can worsen hyperbilirubinemia
and its potential for toxicity, as observed with
ceftriaxone, ibuprofen, benzyl alcohol, and sulfisox-
3,5
azole.
Intravenous (IV) lipid infusions also
100
50
FIGURE 10.2 Percentage of patients with desired and toxic responses as a
function of drug concentration. Therapeutic range is bounded by minimum effective and maximum safe concentrations. MEC, Minimum effective concentration;
MSC, maximum safe concentration.
Efficacy
Toxicity
MEC MSC
can affect the protein binding of both bilirubin
and some drugs, such as nafcillin and ceftriaxone.
The drug concentration measured in most available assays is usually the total drug concentration,
which includes both protein-bound and free forms;
therefore, the available concentration at the receptor (i.e., free drug) usually is somewhat less than
the total serum concentration. This changes over
time for NICU patients with changes in bilirubin
production and changes in the amount and types
of plasma proteins that come with age. The lower
affinity of fetal albumin to weak acids and the
displacement of drugs from binding to albumin
by bilirubin can lead to higher levels of freely
circulating active drugs (e.g., protein binding of
ampicillin, phenytoin, and phenobarbital in neonates is about half of that noted in adults).
40,77
The effect of differences in protein binding on
drug pharmacokinetics can be illustrated using micafungin as an example. Micafungin is an antifungal
agent that disrupts fungal cell walls. It is highly
protein bound and highly metabolized by several
enzymes known to have lower expression in neonates
compared with adults. It would be expected that,
based on decreased metabolizing enzyme activity in
neonates, the elimination of micafungin would be
slower, and lower doses would therefore be needed
in neonates compared with adults. However, pharmacokinetic studies in premature infants demonstrated
that premature infants had 1.7- to 2.6-fold-greater
Соседние файлы в папке Библиотека им академика М.И. Перельмана