Seminars in Pediatric Surgery (2010) 19, 10-19

Clinical assessment of the child with intestinal failure

Jason S. Soden, MD

From the Section of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Colorado Denver School of
Medicine and The Children’s Hospital, Aurora, Colorado.

KEYWORDS The management of the child with intestinal failure is complex, and it is developing into a multispe-
Short bowel cialty field of its own led by expert teams of both transplant and nontransplant surgeons, gastroenter-
syndrome; ologists, and dieticians. Patients are at risk for medical, surgical, and nutritional complications that
Parenteral nutrition should be anticipated so that they can be prevented or managed appropriately. Catheter associated
associated liver infections and intestinal failure associated liver diseases are important complications that impact the
disease; likelihood of bowel adaptation and long-term survival. The clinical assessment of a pediatric intestinal
Citrulline; failure patient should include evaluation of the child within the context of recognized prognostic
Micronutrient factors.
deficiency; © 2010 Elsevier Inc. All rights reserved.
Catheter associated
infection

Intestinal failure (IF) is the end result of any disease state Identification of the underlying disease
that causes chronic dependence on total parenteral nutrition and anatomy
(TPN) to maintain adequate growth, hydration, or micronu-
trient balance. In pediatric patients, the primary etiology of The initial assessment of the infant or child with IF should
IF is short bowel syndrome (SBS) resulting from surgical include identification of the patient’s underlying disease and
resection of the small bowel. The goals in the management anatomy. Table 1 summarizes the etiologies of IF, which
of an IF patient are to provide adequate nutrition for the include SBS, motility disorders, and congenital enteropa-
child to grow and develop normally and to promote bowel thies that lead to chronic malabsorption. SBS is the most
adaptation while monitoring and treating the complications frequent cause of IF in children.1 In a rare setting of an
of the underlying disease and parenteral nutrition (PN). The infant with prolonged TPN requirement and no clear under-
clinical assessment of a pediatric patient with IF must take lying diagnosis, a thorough evaluation for other etiologies
into account an understanding of the patient’s underlying (congenital enteropathy and primary motility disorder)
disease, anthropometric and biochemical evaluation of nu- should be completed. For the neonate with intractable diar-
tritional status, and recognition of the important complica- rhea, evaluation should include endoscopy with careful re-
tions of IF and TPN that limit survival and stratify prognosis view of small intestinal and ultrastructural histopathology.
in the pediatric patient. The assessment of the infant or child with presumed bowel
dysmotility leading to IF requires a complex, coordinated
evaluation that may include specialized motility evalua-
tions.
The significance of identifying the underlying diagnosis
Address reprint requests and correspondence: Jason S. Soden, MD,
Section of Pediatric Gastroenterology, Hepatology, and Nutrition, The Chil-
is relevant in the concept of “irreversible” or “permanent”
dren’s Hospital, 13123 E. 16th Avenue, B290, Aurora, CO 80045. IF. Certain etiologies of IF, including primary enterocyte
E-mail address: Soden.jason@tchden.org. disorders, severe dysmotility states, and potentially long

1055-8586/$ -see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1053/j.sempedsurg.2009.11.002
Soden Assessment of a Child With Intestinal Failure 11

The description of the SBS patient should also summa-

Table 1 Causes of intestinal failure in children
rize relevant anatomic details, with consideration of not
Short bowel syndrome only bowel length but also equally important postsurgical
Neonatal/infants anatomy. Jejunal resection leads to at least a temporary
Atresia
reduction in nutrient absorption, although adaptation of the
Midgut volvulus
Gastroschisis ileum may favor a long-term outcome. High jejunostomy
Necrotizing enterocolitis generally implies a limited absorptive potential. Loss of the
Long segment aganglionosis ileum, subsequently leads to fluid and electrolyte losses, in
Congenital short bowel syndrome addition to bile acid, fat, fat-soluble vitamin, and vitamin
Older children
B12 malabsorption. The presence of the ileocecal valve
Trauma
Mesenteric infarction allows an important anatomic barrier against the reflux of
Radiation enteritis colonic bacteria into the small bowel, and also helps to
Inflammatory bowel disease (rare) regulate the exit of fluids, electrolytes, and nutrients out of
Motility disorders the small bowel.9 The colon itself has important functions in
Primary (congenital)
Neuropathic
improving water and electrolyte absorption, allowing car-
Myopathic bohydrate fermentation and energy absorption via short-
Secondary (acquired) chain fatty acid salvage pathways, and may play an impor-
Neuropathic tant role in promoting adaptation, possibly via its unique
Myopathic microbiota.10 Thus, residual bowel in continuity (eg, jeju-
Mucosal abnormalities
Primary enteropathies
nocolonic vs jejunoileal anastomoses) should be distin-
Microvillous inclusion disease guished anatomically, with implied pathophysiology in
Primary epithelial dysplasia (tufting enteropathy) mind.
Congenital disorders of glycosylation Finally, aside from bowel length and anatomy, assess-
Immune mediated ment of residual bowel function is imperative. Bowel dila-
Primary immunodeficiency syndromes
Autoimmune enteropathies
tion and dysmotility may promote stasis and, secondarily,
small bowel bacterial overgrowth (SBBO), contributing to
malabsorption, translocation/infection, and liver disease.
Furthermore, the presence of SBBO may negatively impact
segment aganglionosis, will not, by current and available bowel adaptation or ability to wean from TPN.11,12 Under-
therapies, adapt or improve.2,3 The pediatric patient with lying diseases, notably gastroschisis, result in dilated, dys-
irreversible IF, therefore, has an expected prognosis of per- functional bowels, despite length and anatomy that would
manent TPN requirement (via current available standards of otherwise be suitable for adaptation. Phillips et al recently
treatment), and referral for evaluation by an intestinal trans- reviewed their experience with neonatal gastroschisis from
plantation center should be considered at an early stage. 1993 to 2007, and identified 9 patients with gastroschisis/
In the setting of a patient with SBS, where the goal in intestinal atresia/dysmotility. These selected patients had
management is to optimize bowel adaptation, the initial adequate postresection small bowel length; however, small
evaluation involves the establishment of a firm understand- bowel dilation and secondary stasis led to significant dys-
ing of the infant’s postsurgical anatomy. Historically, a motility. The survival rate in this group of patients, despite
large emphasis has been on small bowel length, either as adequate bowel length, was only 43%.13 In another series,
length resected or residual length. Infants with a short re- Payne et al14 identified bowel dilation (⬎10 mm) on pre-
sidual bowel length (⬍40 cm) compared with the length of natal ultrasound as a significant factor in predicting infants
with gastroschisis that would develop gastrointestinal com-
⬎100-150 cm of residual small bowel has traditionally been
plications, including atresia, perforation, or resection.
associated with more guarded outcomes. This concept, req-
uisite on absolute bowel length, does not take into account
the dynamic changes in infant bowel length through gesta-
tional development. Small bowel length may double in the
Consideration of predictors of adaptation,
developing fetus (from 19 to 27 weeks gestation as com-
pared to the 35-week gestation, and an increase in average
TPN dependence, and survival in IF
length of 240 cm at birth in the term infant to 380 cm at 12 In general, the diagnosis of IF implies a guarded outcome.
months).4-6 A more accurate description of the bowel length The survival rates for pediatric patients with SBS varies
may include the percentage of bowel resected (or remain- between 73% and 89%, and survival rates for children on
ing) compared to the gestational age-expected bowel chronic TPN has been reported as low as 60%.15,16 For
length.7,8 Thus, the 29 week preterm infant with necrotising patients with irreversible IF, the only therapeutic option
enterocolitis and 20 cm resection may lose a much larger apart from indefinite TPN is bowel transplantation, which
bowel percentage than a term infant with similar absolute still carries significant risks of morbidity and mortality.
length of resection. Transplantation is traditionally reserved for patients with
12 Seminars in Pediatric Surgery, Vol 19, No 1, February 2010

persistent IF, despite attempts at bowel rehabilitation, espe- No discussion regarding the clinical assessment of pedi-
cially those patients with progressive complications or lim- atric IF is complete without mention of the importance of
itations to parenteral therapy. These complications include PN-associated liver disease, referred to in this article as
either recurrent, severe episodes of catheter-associated in- IF-associated liver disease (IFALD). Across the retrospec-
fection (CAI) or limitation of central venous access because tive studies in pediatric IF, the most consistent negative
of venous occlusions and thromboses. Thus, in the clinical prognostic indicator for overall survival is the presence of
assessment of the pediatric patient with IF, it is important to IFALD. IFALD is seen in 40%-60% of pediatric IF patients,
try and stratify each individual patient within the realm of and up to 16.6% may progress to end-state liver disease.26,27
factors that may predict either favorable or poor outcomes. In multiple studies, IFALD is an established predictor of
Because there is a markedly heterogeneous population of patient mortality or PN dependence.21,22,28,29 IFALD is a
pediatric patients with IF as a common end road, the task of multifactorial disease, likely resulting from several factors
predicting outcomes is difficult. Published data are largely unique to the pediatric patient on long-term PN, including
from single center, retrospective studies that are carried out the presence of infection/sepsis, bowel stasis, anatomic fac-
over a number of years with a diverse population of IF tors that affect enterohepatic bile acid circulation, suscepti-
patients, primarily SBS Definitions of SBS and IF have bility of the neonatal liver to cholestatic injury, and factors
varied in published series, and this has led to variability in relevant to the TPN itself that include macronutrient com-
key reported outcomes, such as patient mortality.17 Further- position, contamination/toxicity, and micronutrient excess-
more, as novel therapies are pioneered and used by individ- es/deficiencies.30 Because of the multifactorial etiopatho-
ual centers (including parenteral lipid modification for liver genesis of IFALD, there are no identified single-patient
disease and surgical lengthening procedures), individual factors that would uniformly predict occurrence or severity
patient factors that were, in previous years, more static (for of the disease. Age may be an important predicting factor
instance, residual small bowel length and presence of per- for liver disease, in that neonatal patients are more likely to
sistent cholestasis), may be considered more dynamic vari- develop aggressive, cholestatic liver disease in contrast to
ables in the current era. the histologic steatosis seen in adults.30,31 Sepsis is also an
With these limitations of the available, retrospective data important cofactor for the development of IFALD, and
in mind, the clinical assessment of the patient with IF should retrospective studies have illustrated that the timing (early
be performed with consideration of the factors that predict onset) and frequency of CAI in SBS predict both the oc-
successful or poor outcomes. Table 2 highlights some of the currence and severity of IFALD.27,32 Andorsky et al18 have
key positive and negative prognostic factors in pediatric demonstrated the advancement of enteral nutrition (or dis-
SBS and IF that have been identified by recent retrospective continuation of TPN) to be an important factor in predicting
studies.7,15,18-22 Regarding the SBS patient’s postsurgical the reversal of biochemical cholestasis. Thus, the clinical
anatomy, the residual length of the small intestine, presence assessment of the child with IF requires establishment of
of ileocecal valve or colon, and establishment of intestinal risk factors for IFALD development, and when indicated,
continuity have all been demonstrated relatively consistent defining the presence and severity of liver disease.
to help predict the ability to wean PN.3,23,24 In separate
retrospective analyses, residual bowel length of ⬎15-40 cm
or ⬎10% of actual small bowel length at the time of resec-
tion have been associated with a high prediction of success- From retrospective data to the clinical
ful adaptation.19,21,22 The percentage of daily kilocalories assessment of the patient with IF
provided enterally at 6, 12, or 24 weeks may provide pre-
The management of the pediatric patient with IF entails a
dictive information about the ability to wean of TPN.18,25
balance between promotion of growth/bowel adaptation
Other patient factors, including the underlying disease (gas-
versus recognition and treatment of the complications of
troschisis), prematurity, or other systemic complications
IF/SBS and TPN therapy. Table 3 summarizes the compli-
may affect patient prognosis.
cations seen in IF patients. In general, the most severe
complications are those related to the necessity to provide
TPN. Complications of the underlying disease, especially in
Table 2 Predictors of outcomes in pediatric SBS and IF
SBS, are dependent on the child’s anatomy, enteral intake,
Positive factors Negative factors and other factors. The assessment of the IF patient requires
Residual bowel length ⬎ Residual bowel length ⬍ 15-20
a generalized understanding of these complications so that
35-40 cm cm or ⬍ 10% age-expected problems can be identified and managed aggressively.
normal
Presence of ICV or colon Prematurity/neonates
Older infants/children Presence of persistent liver
disease Assessment of nutritional and fluid status
Presence of bacterial overgrowth
Underlying disease: gastroschisis Clinically, the first task in assessment is to ascertain the
child’s nutritional status. Accurate measurements of weight,
Soden Assessment of a Child With Intestinal Failure 13

electrolytes. Gastrointestinal fluid and electrolyte losses

Table 3 Complications in the management of the IF
patient vary depending on losses from nasogastric tubes, gastros-
tomy tubes, or enterostomy output. Fluid and electrolyte
Complications related to Complications related to SBS management is an integral part of TPN management, and
TPN therapy or underlying disease
serum electrolyte levels should be monitored routinely.
Intestinal failure–associated Malabsorptive Urine sodium level is traditionally a more accurate estimate
liver disease Growth failure of total body sodium content, and a low urine sodium
Fluid, electrolyte, Fluid, electrolyte, (⬍10-20 mmol/L) may detect sodium depletion earlier than
micronutrient micronutrient
serum values.4,35
imbalances Deficiency states
Catheter-associated Diaper/stoma skin breakdown In a child who has been on long-term PN, or graduated
problems Bone demineralization successfully from TPN, periodic surveillance of micronu-
Infection/sepsis Medication/pharmacologic trient status is recommended. Recommendations regarding
Thrombosis D-lactic acidosis parenteral supply of minerals and trace elements have been
Mechanical/breakage Nephrolithiasis published.36 For the child on long-term TPN, iron defi-
Motility disturbances ciency may occur, and laboratory indications of iron status
Mechanical obstruction
(ferritin, iron level, and iron-binding capacity) should be
Bacterial overgrowth
Gastric acid hypersecretion
followed. Dahlstrom et al37 demonstrated that patients on
GI mucosal long-term PN had decreased levels of serum trace elements
Noninfectious colitis compared to age-matched controls; however, no clinical
Anastomotic Ulcerations signs or symptoms of deficiencies were detected. Fluctua-
Cholelithiasis tions in serum levels of copper, zinc, manganese, and lead
were reported during TPN administration in a group of adult
patients.4,38 Other trace elements, including chromium, cop-
height, and head circumference are critical, and these should per, zinc, and selenium should also be periodically moni-
be compared with standardized normal values. Plotting tored.36 Zinc deficiency may occur in patients with gastro-
along normative growth curves should be corrected for intestinal fluid losses, and therefore zinc levels should be
gestational age in the former premature infant. Growth data monitored. Selenium, an important antioxidant, has been
should be measured, recorded, and compared with each shown in various deficiency states in chronic TPN patients.
individual patient’s own medical history data. Fluid shifts, Useful biomarkers of micronutrient and trace mineral status,
changes in stool and ostomy output, ascites, and bowel wall including copper, zinc, selenium, and iodine need further
edema may alter the ability to rely on weight values alone. analyses to validate the optimal assays and cutoff values,
Reliance on weight or weight/height alone may underesti- particularly in infants and children.39-43
mate the degree of acute malnutrition in children with Standard PN formulations routinely contain vitamin
chronic liver disease, due to inflated patient weight caused packages, and guidelines on recommended dosing have
by organomegaly.33 Therefore, assessment of body compo- been published.36 There is insufficient evidence to support
sition by measuring midarm circumference and triceps skin- the routine measurement of serum vitamin levels in all
fold thickness is important, especially in the child with fluid patients with IF that are on long-term TPN. However, cer-
shifts or IFALD. tain disease states, especially cholestasis and pancreatic
In a retrospective series of 87 patients with SBS and IF,
insufficiency, may predispose the patient with IF to greater
9 patients remained on chronic PN and had a mean body
fat-soluble vitamin losses, and surveillance of fat-soluble
weight of ⫺0.5 ⫾ 0.64 SDS and height of ⫺0.75 ⫾ 0.99
vitamin levels in these patients is advised. Measurement of
SDS. Twelve patients were weaned off PN, but because of
water-soluble vitamin levels should be obtained in the child
the failure to maintain adequate linear growth, PN was
on continuous PN therapy, if a clinical deficiency syndrome
restarted. SBS patients who were successfully weaned from
all artificial enteral and PN support (n ⫽ 57) achieved is suspected. In the long term follow-up of IF and SBS,
normal long-term growth and pubertal development.19 Sim- patients who have graduated from TPN, micronutrient de-
ilarly, in a small retrospective series, Wu et al34 verified ficiencies are common and should be surveyed clinically via
normal anthropometric measurements, weight for age, and laboratory studies.34,44,45 The expectation of when to pre-
height for age in 9 patients weaned from PN for more than dict micronutrient deficiencies in a patient who has been on
2 years. In summary, normal growth may be achieved on long-term PN is not well-established, and more studies are
PN, and patients successfully weaned from PN may have required to clearly define the timing of laboratory evalua-
normal long-term growth. However, the anthropometric sta- tions if clinical deficiency syndromes are not suspected. In
tus should be followed up very closely in the period during general, one should direct the laboratory evaluation toward
and after PN weaning. monitoring for expected micronutrient deficiencies Table 4
Assessment of fluid status includes estimation of the outlines important minerals and vitamins to follow in the
patient’s hydration status, stoma/stool losses, and serum clinical assessment of the pediatric patient with IF, includ-
14 Seminars in Pediatric Surgery, Vol 19, No 1, February 2010

Table 4 Micronutrient deficiency or overload syndromes in intestinal failure

Clinical deficiency Clinical overload

Micronutrient Pathophysiology syndrome syndrome Laboratory evaluation
Minerals and trace
elements
Calcium Fat malabsorption Paresthesias, tetany, bone *GI, GU, bone complaints Serum Ca, PTH, DEXA
demineralization scan
Magnesium Fat malabsorption and high Weakness, cardiac, CNS *Weakness, cardiac Serum Mg
GI fluid losses
Zinc GI fluid losses Poor growth, skin, hair, *Vomiting, headache, Serum Zn, low alkaline
diarrhea diarrhea, Cu deficiency phosphatase
Copper Overload more common in *Hemolytic anemia, Hepatic overload, Serum Cu
cholestasis neutropenia neuropsychiatric
Manganese Overload more common in *Poor growth, ataxia, Neurotoxicity Serum Mn
cholestasis skeletal
Iron Absorbed proximally; not Microcytic anemia, Hepatotoxicity, GI bleeding, Ferritin, TIBC, Iron
routinely in TPN irritability vomiting Binding Cap, Hgb,
HCT, peripheral smear
Selenium Absorbed throughout small Myopathy, cardiomyopathy *Thyroid enlargement Serum selenium
bowel
Fat-soluble
vitamins
A Fat malabsorption, Xerophthalmia, blindness Increased ICP, hepatitis, Vitamin A: retinol
cholestasis vomiting binding protein ratio
D Fat malabsorption, Hypocalcemia, Emesis, renal impairment 25-OH vitamin D
cholestasis hypophosphatemia, rickets
E Fat malabsorption, Myopathy, neuropathy, coagulopathy Vitamin E: total
cholestasis ataxia, hemolytic anemia serum lipid ratio
K Fat malabsorption, Bleeding Hemolytic anemia Prothrombin time,
cholestasis PIVKA assay
Water-soluble
vitamins
B12 Gastric or ileal resection Megaloblastic anemia, CNS None known Serum B12,
including ataxia methylmalonic acid,
homocysteine
Folate Absorbed proximally Anemia, thrombocytopenia, None known Serum Folate
stomatitis, glossosis
*Rare in pediatric intestinal failure.

ing summary of clinical deficiency syndromes and recom- gical bowel length and anatomy in the SBS patient has been
mended laboratory evaluations. previously emphasized, and the physical and radiographic
In patients who receive parenteral lipid therapy, serum examinations may help to assess bowel dilation, motility,
triglyceride levels should be routinely followed up. Surveil- and length. In the setting of SBS or primary motility disor-
lance for essential fatty acid deficiency is advised for pa- ders, abdominal radiographs may demonstrate dilated loops
tients who are either on omega-3 fatty acid-based lipid of a small bowel. Air fluid levels may be demonstrated in
solutions or with significant fat malabsorption that have areas of mechanical obstruction, or in chronic intestinal
been weaned off parenteral lipids,. Essential fatty acid de- pseudo-obstruction. Other objective evaluations of bowel
ficiency may present clinically in an infant with sparse hair, motility including manometry and transit studies may pro-
poor weight gain, poor wound healing, and thrombocytope- vide insight into pathophysiology or bowel function in sus-
nia, and laboratory evaluation confirms an elevated ratio of pected primary motility disorders with IF.47 Patients with
eicosatrienoic acid: arachidonic acid (triene: tetraene).46 SBS may have disordered motility due to the disruption in
normal neuroendocrine patterns in the postsurgical bowel.
When indicated, contrast radiology may be used as a clinical
Assessment of bowel length and function tool to assess dilation, motility, and length. Nightingale et
al48 reported a high correlation between radiographic and
Along with the nutritional evaluation of the IF patient, the surgical measurements of small bowel length in 18 adult
clinical assessment should involve an estimation of the SBS patients. Recently, Rossi et al49 reported their experi-
child’s residual bowel function. The relevance of postsur- ence in estimation of small bowel length on radiological
Soden Assessment of a Child With Intestinal Failure 15

films with a hand-held opisometer, and they were able to serves as an indicator of bowel adaptation, in which enteral
correlate objective evidence of bowel growth by this advancement and parenteral weaning are generally propor-
method with bowel adaptation and ability to wean off PN in tional. Since 100% enteral adaptation is the ultimate goal in
8 pediatric patients. IF management, one must carefully assess the patient’s
Apart from estimation of bowel length and motility, enteral access. Frequently, the patient with IF requires con-
estimation of bowel dilation by GI contrast series may play tinuous feeding, generally via a gastrostomy tube, to opti-
a role in predicting the important pathophysiologic conse- mize both absorption and adaptation. Alternative enteral
quences of bacterial overgrowth. Stagnant, dilated loops of access routes, including gastrojejunal tubes or direct jejunal
bowel, especially in the setting of a patient with an entero- feeding tubes are considered in the setting of gastric or
colonic anastomosis, may precipitate small intestinal bacte- proximal bowel dysmotility and feeding intolerance. A sec-
rial overgrowth. Figure 1 demonstrates pathologic small ondary goal in clinical management is for pediatric IF pa-
bowel dilation in a patient with SBS and IF. Objective tients to achieve both oral and enteral autonomy, without
assessment for small intestinal bacterial overgrowth in- dependence on supplemental enteral support. Oral aversion
cludes hydrogen breath testing or quantitative culture from
and feeding difficulties are relatively common in the pedi-
small intestinal fluid, although the clinical utility of these
atric IF population, namely due to chronic dependence on
evaluations in the management of pediatric IF and SBS
nutritional support since the neonatal period. Thus, the clin-
remains controversial. Furthermore, in the present era,
ical assessment should include evaluation of enteral caloric
where nontransplant surgical intervention may be consid-
intake as an indicator of adaptation and bowel function, and
ered to relieve intestinal dysmotility and promote intestinal
lengthening and adaptation, demonstration of adequate should also be focused on appreciation of enteral access and
bowel dilation on GI contrast series may at least provide a oral feeding skills and progress.
road map of the therapeutic possibility of these surgical Recently, serum or plasma citrulline levels have been
“steps.” identified as a potential biomarker of functional enterocyte
A direct correlate to bowel function is the assessment of mass. Citrulline is a nonessential amino acid produced pri-
a child’s enteral progress. Sondheimer et al25 reviewed their marily in the enterocyte by the metabolism of glutathione
experience in 27 infants with SBS and IF and found that the and praline. Several studies have correlated circulating cit-
percentage of daily calories provided enterally at 12 weeks rulline level with functional small bowel enterocyte mass
adjusted age significantly correlated with the duration of and absorptive capacity.50-59 Table 5 highlights recent stud-
TPN dependence. Therefore, progress in enteral nutrition ies involving citrulline levels in pediatric patients with SBS.
Data available from the clinical utility of this assay are
promising, and warrant further investigation.

Assessment of critical complications

of TPN therapy
Despite the meticulous management of nutrition, fluids, and
electrolytes, as well as proactive measures to assess and
promote bowel adaptation, life-threatening complications of
parenteral therapy are unavoidable in most IF patients. In a
retrospective cohort of 302 pediatric patients receiving
home PN, the mortality rate in children with primary diges-
tive disorders was 9%. Of this subset, 48% died of either
liver disease or sepsis.60 Similarly, Wales et al17 identified
a mortality rate in 37.5% of a cohort of 40 infants with SBS
(defined as bowel length ⬍25% age-expected normal, or
TPN ⬎6 weeks), with most deaths occurring from liver
disease and sepsis. Because of the cause-and-effect interre-
lationship between infection and liver disease in TPN pa-
tients, and their important impact on patient survival, these
complications should be evaluated vigilantly. Furthermore,
in the assessment of the child with IF and either recurrent
Figure 1 Upper gastrointestinal with small bowel follow-through
series in a child with short bowel syndrome and an ileorectal anastomosis. life-threatening infections or progressive liver disease, re-
Note the dilated loops of bowel which contribute to the clinical presen- ferral to a center with experience in aggressive bowel reha-
tation of abdominal distension, bloating, enteral intolerance, and bacterial bilitation, PN modification strategies, or bowel transplanta-
overgrowth in the patient. tion should be considered.
16 Seminars in Pediatric Surgery, Vol 19, No 1, February 2010

Table 5 Citrulline as a biomarker for functional enterocyte mass in pediatric SBS

Study Patient characteristics Design Conclusions

Rhoads, et al58
SBS infants (n ⫽ 24); Serum CIT levels in 4 groups: Serum CIT ⬎ 19 umol/L is
age-matched controls control, off TPN, weaned associated with development of
(n ⫽ 21) TPN, on TPN enteral tolerance
Jianfeng, et al59 SBS children (n ⫽ 22); Correlation with small bowel Serum CIT levels correlated well
age-matched controls radiographic measurements with remnant small bowel length,
(n ⫽ 33) and absorption assays surface area, 5-h urine D-xylose
excretion, and digestive protein
absorption
Bailly-Botuha, et al56 SBS children (n ⫽ 31) Prospective plasma citrulline Baseline plasma CIT ⬍ 11 umol ⫹
assays correlating with bowel length ⬍ 50 cm is associated
ability to wean TPN with PN dependence
Fitzgibbons, et al55 SBS children (n ⫽ 27) Retrospective analysis of Plasma CIT ⬎ 15 micromol/L
plasma CIT correlating with predicts patients that will wean
ability to wean TPN off TPN (sensitivity ⫽ 89%;
specificity ⫽ 78%)

Catheter associated complications, assistance in localization of access sites, or referral to a

including infection center with a team skilled at complicated vascular access.67

Because the provision of TPN is dependent on a functioning, IF associated liver disease

central venous catheter (CVC), complications related to the
CVC in the IF patient are relatively common and important to Because of its importance in prognosticating the IF patient’s
assess and manage. In a retrospective series of 60 pediatric IF course, the clinical assessment must define the presence and
patients in Italy, prevalence of CAI was 1.4/1000 CVC days, severity of liver disease. Biochemically, elevated transami-
and thromboses occurred at a prevalence of 0.2/1000 CVC nases and bilirubin are common in infants on PN, but typically
days.61 Potential sources for CAI include infection from the resolve in short-term TPN courses. Persistent cholestatic injury
skin at the time of placement, luminal infection during con- is characterized by progressive/persistent elevation in bilirubin,
nection/disconnection, seeding from a distal site, or contami- transaminases, and gamma-glutamyl transpeptidase. His-
nation.62 In IF patients, SBBO, immune dysfunction, compro- topathologic features include cholestasis, bile duct prolifera-
mised bowel permeability, and liver disease may predispose tion, periportal inflammation, and fibrosis.68 Ultimately, se-
for the translocation of enteric bacteria into circulation, creat- quelae of chronic liver disease arise in patients with persistent
ing a set-up for catheter colonization or sepsis. In 1992, Kurk- PN requirement and progressive injury. These complications
chubasche et al63 determined a 6-fold increase in the incidence include cirrhosis, portal hypertension, coagulopathy, and on-
of catheter sepsis events in pediatric SBS patients compared going risks of bleeding and death.26,30 Weber and Keller28
with non-SBS patients. SBS patients are also more likely to correlated the severity of liver disease (by child’s classifica-
have gram-negative infections compared to other patients with tions) with negative indicators of bowel adaptation (prolonged
indwelling CVC, and patients with a shorter bowel are more time to feed, total TPN time).
likely to develop CAI.64,65 Thus, infection should be consid- The laboratory assessment of the patient with IFALD
ered with a high index of suspicion in the clinical assessment should include hepatobiliary enzymes and routine monitor-
of the IF and SBS patient that presents with either typical ing of liver function (prothrombin time) and interval sur-
presenting signs (fever, lethargy, and shock) or atypical symp- veillance for fat-soluble vitamin deficiency. The examiner
toms (irritability and change in baseline stool/stoma output). should carefully evaluate evidence of portal hypertension
The occurrence of catheter associated infection may lead (splenomegaly, ascites, and hypersplenism with thrombocy-
to further complications in the patient’s parenteral therapy. topenia). When accessible (for instance, during surgery for
Despite antimicrobial therapy, catheter salvage only occurs stoma closure or revision), a liver biopsy should be obtained
in 42%-52% of patients with CAI.63,66 Apart from sepsis, for evaluation and follow-up of histologic injury. Recently,
other mechanical and thrombotic complications may occur the (13)C-methionine breath test has been evaluated in a
that require CVC removal. Impaired central venous access small cohort of patients as a potentially noninvasive and
that is an indication for bowel transplantation, frequency of reliable measure of liver function in children with IF.69
infections, or mechanical problems should be carefully as- Other noninvasive serum biomarkers and imaging modali-
sessed in each patient, taking into account any pending loss ties to assess liver fibrosis have not yet been evaluated in the
of venous access. Patients who are at risk for loss of central setting of IFALD, but may potentially have important roles
venous access may require sonography or venography for in the future.70,71
Soden Assessment of a Child With Intestinal Failure 17

Other complications in the pediatric IF patient ical outcomes, including liver disease. Referral to a center
with nutritional, medical, and surgical expertise in the mul-
Key features of the clinical evaluation of the IF patient have tispecialty care of these complex patients is advised. More
been addressed thus far, including assessment of nutritional studies into novel and potentially noninvasive diagnostic
status, residual bowel function, enteral tolerance and access, tools are warranted, and prospective, multicenter studies are
infection rate, catheter access, and liver disease. Long-term needed to better assess relevant outcomes and therapies.
follow-up of the patient requires an ongoing assessment of
these key areas, in addition to awareness of other compli-
cations that may occur.
Metabolic bone disease has been reported in pediatric References
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