In T.C.’s case, the dextrose concentration will begin and continue at 10% because

of the peripheral catheter limitations. This concentration will provide 7.3

mg/kg/minute. If a central catheter later becomes necessary, the concentration can be

increased by 5% each day until the caloric requirement is met. This increase should

be accompanied by blood and urine glucose monitoring. If the blood glucose is 150

mg/dL or greater, or if the urine glucose exceeds “trace” amounts, the PN infusion

rate should be decreased by at least 25% and a second IV solution should be added

to provide needed fluids and electrolytes. Alternatively, the dextrose concentration

can be decreased or insulin can be infused concomitantly and titrated to a desired

serum glucose concentration of 120 to 140 mg/dL.

Fat emulsion should be initiated at 1 g/kg/day and increased daily by 0.5 to 1

g/kg/day until the maximal dosage of 3 g/kg/day is reached. The daily fat dose should

be infused at a constant rate because fats are better tolerated when infused over the

course of 24 hours.

27 Serum triglycerides should be monitored every other day while

the dose of fat is being increased. Patients with a fasting triglyceride concentration of

150 mg/dL or less may have their fat dose increased. In patients who are receiving

inadequate calories, triglycerides may be elevated because endogenous fats are being

mobilized. If the triglyceride concentration is greater than 150 mg/dL, the serum

sample must be examined visually. A clear sample with a mildly elevated

triglyceride concentration probably indicates the use of endogenous fat stores for

energy. Conversely, a turbid or lipemic sample indicates the patient’s inability to use

the amount of intravenous fat administered. In this case, further increases in the fat

dose should be delayed until triglyceride concentrations decrease.

Special Considerations and Complications

CASE 103-7

QUESTION 1: J.H., a 4-day-old boy, was born at 31 weeks’ gestation. His birth weight was 1,950 g, and he

now weighs 2,000 g. On the first day of life, he was given a commercial preterm infant formula by orogastric

tube in gradually increasing quantity with supplemental IV fluids. Now, on the fourth day of life, he has a

distended abdomen and his stools contain bright red blood. An abdominal radiograph shows pneumatosis

intestinalis (gas within the intestinal wall seen on X-ray). All enteral feedings are stopped (NPO). What do

these findings represent? What are the implications for J.H.’s nutritional management?

Abdominal distension, bloody stools, and pneumatosis intestinalis are

characteristic of necrotizing enterocolitis historically.

28 The causes of this disorder

are unclear, but it occurs more often in premature than in term infants; it can occur in

clusters of cases, rarely is seen before enteral feeding is instituted, and can be

associated with rapid increases in enteral intake.

29 Because J.H. will receive

antibiotics for 10 to 14 days and remain NPO, he requires PN. The planned duration

of the regimen makes central venous access a necessity.

GOALS OF LONG-TERM SUPPORT

CASE 103-7, QUESTION 2: The following day, intestinal perforation requires the resection of two-thirds of

J.H.’s distal jejunum and one-third of his ileum, with creation of a jejunostomy. The ileocecal valve and the

entire colon are left intact. During the operation, a central venous catheter is placed. What is the goal of PN for

J.H.?

J.H. will be NPO for a prolonged time. Therefore, the goals of his PN must be to

promote normal growth as well as healing of his diseased gut and surgical wounds.

Because J.H. is a premature infant, it will be difficult to predict how well he will

tolerate PN. VLBW infants tolerate normal doses of pediatric amino acids without

difficulty; however, some clinicians initiate protein at a lower daily dose (e.g., 1.0

g/kg/day) and advance by 0.5 g/kg/day each day until a goal of 2 to 3 g/kg/day is

achieved. Fat should be started at 0.5 to 1 g/kg/day and increased by 0.5 g/kg/day up

to 3 g/kg/day. Glucose should be initiated at 5 to 10 g/kg/day and increased by 2 to 3

g/kg until the desired caloric intake is achieved. Appropriate doses of electrolytes

and minerals may be started immediately using the guidelines listed in Table 103-1.

FAT EMULSIONS: COMPLICATIONS

CASE 103-7, QUESTION 3: What must be considered in making decisions regarding fat administration in

J.H.?

Although J.H. can receive adequate calories using only glucose and crystalline

amino acids, he will require fat to provide a more physiologic diet and to prevent

essential fatty acid deficiency (EFAD), which develops quickly in low-birth-weight

infants who have little fat reserve. J.H. should receive a minimum of 5% of his total

caloric requirement as fat emulsion to minimize the risk of EFAD. Ideally, his

nutrition regimen will provide approximately 40% of calories from fat, which is

similar to what is provided by human milk.

Infusions of fat emulsion have been associated with impaired oxygen transport and

pulmonary ventilation–perfusion mismatch. This adverse effect occurs more often

when the dose of fat is 4 g/kg or greater and is infused for a relatively short (4 hours)

period. Current practice is to increase gradually the doses of fat from 0.5 to 1

g/kg/day up to a maximum of 4 g/kg/day and to infuse the fat emulsion over the course

of 24 hours to minimize the likelihood of pulmonary problems and to promote

clearance.

It is unclear whether IV fat administration is detrimental to patients with sepsis.

Infusion of fat emulsion has resulted in lymphocyte and neutrophil death.

30 On the

other hand, the linoleic acid in IV fat is the precursor to arachidonic acid,

prostaglandins, thromboxane, interleukins, and immune-mediating cells.

Theoretically, this may minimize bacteremia. Necrotizing enterocolitis, intestinal

perforation, and surgery predispose J.H. to sepsis. Therefore, he should have his IV

fat infused at an appropriate dose over the course of 24 hours. Because fat clearance

can be impaired during infection, it is also prudent to monitor his triglyceride

concentrations.

Free fatty acids can displace bilirubin from its albumin binding sites, thereby

placing the infant at risk for kernicterus.

31 Therefore, before advancing the fat dose,

the total bilirubin and direct bilirubin should be measured. Patients with an indirect

bilirubin (total bilirubin minus direct bilirubin) of 10 mg/dL or less whose albumin

levels are normal are at low risk for kernicterus. Indirect bilirubin usually peaks

before 1 week of age. After the risk for indirect hyperbilirubinemia has passed, the

fat dose can be increased as recommended in Table 103-1. The infusion of 1 g/kg

over the course of 24 hours is associated with minimal risk for decreased bilirubin

binding

31

; however, rapid infusion of this same dose can displace bilirubin from

albumin binding sites. Given the low level of indirect bilirubin found on routine

monitoring and the planned fat infusion rate, J.H. should not be at risk for kernicterus.

Egg phospholipids are used to emulsify fats; therefore, patients with a known

allergy to eggs (e.g., fever, chills, urticaria, dyspnea, bronchospasm, chest pain)

should not receive fat emulsion.

p. 2149

p. 2150

GLUCOSE INTOLERANCE

CASE 103-7, QUESTION 4: Because J.H. is a premature infant, PN is initiated using 5% glucose, 2.5

g/kg/day of amino acids, and 0.5 g/kg/day of fat emulsion. The volume of PN should be 240 mL based on a

maintenance fluid requirement of 120 mL/kg (Table 103-1). On the second day, he receives 10% glucose, 2.5

g/kg/day of amino acids, and 1 g/kg/day of fat. On the third day, glucose is increased to 15%, amino acids

remain at 2.5 g/kg/day, and fat emulsion is increased to 1.5 g/kg/day. On the fourth day, glucose is increased to

20%, amino acids remain at 2.5 g/kg/day, and fats are increased to 2 g/kg/day. After this solution has been

infused for 8 hours, his urine test yields 1% for glucose (normal, no glucose) and his blood glucose level is 210

mg/dL (normal, 120 mg/dL). Explain this new finding and the problems it may cause. How should

hyperglycemia be managed?

Maximal glucose oxidation rates in milligrams per kilograms per minute are

inversely related to age and decrease from 15 to 18 mg/kg/minute in neonates and

young infants to 4 to 5 mg/kg/minute in adults. In full-term neonates and infants

receiving maintenance fluids (100 mL/kg/day), glucose concentrations can be started

at 10 g/kg/day (equivalent to dextrose 10%) and advanced by 5 g/kg (equivalent to

dextrose 5%) every 24 hours up to approximately 25 g/kg/day (equivalent to dextrose

25%). In preterm neonates, such as J.H., dextrose is started at a lower dose and

advanced at smaller increments, usually 2 to 3 g/kg/day. Glucose tolerance varies

significantly, so each patient should be considered individually.

At J.H.’s prescribed fluid rate of 10 mL/hour, 20% glucose represents 16.7

mg/kg/minute of glucose. The hyperglycemia and glycosuria probably have occurred

because the increases in the infusion rate have exceeded J.H.’s ability to adapt to the

glucose dose. Patients who have been euglycemic on their glucose dose and then

become glucose intolerant should be evaluated, however, for other causes, such as

infection and addition of exogenous corticosteroids. Hyperglycemia and glycosuria

can result in serum hyperosmolarity, osmotic diuresis, and dehydration. Regardless

of the cause, the hyperglycemia should be treated by reducing the glucose

administration rate. The rate of the PN infusion can be decreased further if

hyperglycemia continues or increased if the hyperglycemia resolves.

When the PN order is written for the subsequent days, the glucose increases should

be made in smaller amounts up to the full daily maintenance calorie requirements.

Frequent blood and urine glucose monitoring must be continued. Severe glucose

intolerance in patients who require PN can be managed with insulin to normalize

serum glucose. Although insulin is compatible with PN solutions, it does adsorb to

glass, polyvinyl chloride, and filters, resulting in decreased delivery of insulin.

32

Frequently, pediatric patients have changing insulin requirements that prevent the

addition of insulin to PN solutions. A separate continuous infusion of regular insulin

(initial dose, 0.05–0.1 units/kg/hour) titrated to control serum glucose concentrations

offers a practical solution to minimize waste of the PN solution.

33

It is essential to

discontinue the insulin infusion if the PN solution is discontinued to avoid

hypoglycemia.

EFFECTS OF BRONCHOPULMONARY DYSPLASIA AND MECHANICAL

VENTILATION

CASE 103-7, QUESTION 5: J.H. remains dependent on a ventilator because of his immature lungs. How

could J.H.’s respiratory disease influence his nutritional regimen?

After 28 days of age, J.H.’s ventilator dependence defines him as having

bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy. Historically,

BPD is characterized by an increase in resting energy expenditure, increased work of

breathing, and growth failure.

34,35 Therefore, J.H.’s caloric requirement may be

higher than expected. Additionally, J.H.’s ventilator may also alter the approach to

his caloric supply. Very high carbohydrate loads have been associated with an

increase in carbon dioxide production.

36 This, in turn, may make it difficult to wean

J.H. from the mechanical ventilator. As discussed, rapid infusions of fat emulsion can

also have a detrimental effect on pulmonary function. Fat emulsion should not be

omitted from J.H.’s PN regimen; rather, a slower infusion rate, with gradual dose

increases, while monitoring pulmonary function is appropriate.

PEDIATRIC AMINO ACID FORMULATIONS

CASE 103-7, QUESTION 6: Why would a specialized pediatric amino acid solution be preferable to a

standard adult formulation for J.H.?

Patients 1 year of age or older tolerate standard adult amino acid preparations

(e.g., Aminosyn and Travasol) well. For infants, two specifically designed pediatric

amino acid formulations (PAAFs)—TrophAmine and Aminosyn PF—are available.

PAAFs were developed in response to the abnormal plasma amino acid patterns

noted in infants receiving adult amino acid formulations. The products were designed

with the goal of producing plasma amino acid patterns closely matching those of 2-

hour postprandial, human milk-fed infants. Theoretically, normal plasma amino acid

patterns will promote normal protein synthesis in growing infants.

Pediatric amino acid formulations differ from conventional amino acid

formulations in several ways. First, they contain a higher content of branched-chain

amino acids (leucine, isoleucine, and valine) and a lower content of glycine,

methionine, and phenylalanine. In addition, PAAFs have a higher percentage of

essential amino acids with a wider distribution of the nonessential amino acids.

Finally, PAAFs are unique in that they contain three essential amino acids for

neonates: taurine, tyrosine (as N-acetyl-L-tyrosine), and cysteine (added as Lcysteine HCl). Adult solutions contain little if any of these amino acids. Neonates

have immature liver functions. This results in decreased levels of both hepatic

cystathionase and phenylalanine hydroxylase enzymes. Without these enzymes,

neonates cannot adequately convert methionine to cysteine or phenylalanine to

tyrosine or synthesize taurine from cysteine. Deficiencies in these amino acids can

have a significant impact on the health of the neonate. For example, taurine has a role

in retinal development, protection and stabilization of cell membranes,

neurotransmission, regulation of cell volume, and bile acid conjugation. Taurine also

may be important in decreasing or preventing cholestasis associated with long-term

PN.

Several investigators have studied the clinical, nutritional, and biochemical effects

of TrophAmine in term and preterm infants.

37,38 The use of TrophAmine was found to

result in nearly normal amino acid patterns. In addition, patients receiving

TrophAmine had greater weight gain and significantly better nitrogen utilization than

similar groups using the adult formulations. TrophAmine and Aminosyn-PF, given for

a 7-day period, produced comparable weight gain and nitrogen retention.

39

In one

study, some of the VLBW infants experienced metabolic acidosis.

37 L-Cysteine, an

HCl salt, provides an additional 5.7 mEq of chloride/100 mg and may have

contributed to the acidosis. Whereas the manufacturer’s recommended dose of 40 mg

of L-cysteine per gram of amino acid may be too much for the VLBW infant, the most

appropriate dose of L-cysteine for the VLBW infant has not been determined.

p. 2150

p. 2151

To date, PAAFs have been effective in producing a positive weight gain and

positive nitrogen balance, and normalizing amino acid patterns in preterm neonates.

They also allow for the provision of larger doses of calcium and phosphorus because

PAAFs lower the pH of the final PN solution. Providing greater amounts of calcium

and phosphorus, in appropriate ratios, should minimize metabolic bone disease.

Further evaluation of these products is needed to determine the magnitude of the

proposed benefits (i.e., improved nitrogen retention, better weight gain, enhanced

bone growth, and decreased cholestasis) and the most appropriate L-cysteine dose to

use in VLBW infants. In any event, these potential benefits, and clinical experience

with these products, have resulted in the use of PAAFs as the standard of care in

infants requiring PN.

CARNITINE

CASE 103-7, QUESTION 7: Why would carnitine supplementation be warranted in J.H.?

Carnitine has many functions within the body, but it primarily serves to transport

long-chain fatty acids (LCFA) across the mitochondrial membrane where they

undergo β-oxidation to produce energy. Deficiency in carnitine lessens LCFA

availability for oxidation, resulting in the accumulation of LCFA and a decrease in

ketone and adenosine triphosphate (ATP) production. This can adversely affect the

CNS and skeletal and cardiac muscles. Carnitine deficiency in premature infants also

has been linked to disorders such as GI reflux, apnea, and bradycardia.

40

Whereas carnitine is a nonessential nutrient in adults and is readily available from

a diet that includes meat and dairy products, it appears to be an essential nutrient in

neonates and infants. This population has low body stores of carnitine and a

decreased ability to synthesize it on their own. The premature infant has even lower

stores because carnitine accumulation occurs during the third trimester. Human milk

and most cow’s milk-based infant formulas contain carnitine. Some soy-based

formulas have additional carnitine added during manufacturing. PN, however, is not

routinely supplemented with carnitine. Therefore, infants who are exclusively fed by

PN are at risk for developing complications associated with carnitine deficiency.

40

Because J.H. has two risk factors for the development of carnitine deficiency

(prematurity and exclusive use of PN), and because carnitine has little or no adverse

effects associated with its use, it is appropriate to provide J.H. with a carnitine

supplement. Carnitine is available as both an oral and IV formulation. The

recommended dose in J.H. is 10 to 20 mg/kg/day. The addition of carnitine directly

to PN improves carnitine plasma concentrations and nutritional status.

METABOLIC BONE DISEASE (RICKETS)

CASE 103-7, QUESTION 8: On the chest radiograph taken to evaluate the septic episode just described, the

radiologist notes that J.H. has two rib fractures and that the bones appear undermineralized. The most recent

laboratory values show a serum calcium (Ca) of 9.3 mg/dL (normal, 8.5–10.5 mg/dL), a serum phosphorus of

3.6 mg/dL (normal, 4.0–8.5 mg/dL), and an alkaline phosphatase of 674 units/L (normal, 350 units/L). What

diagnosis is suggested by these findings? How and why has J.H.’s nutrition regimen placed him at risk for this

disease?

During the last trimester of pregnancy, bone accretion is accelerated, reaching its

peak at about 36 weeks. Premature infants, therefore, require larger calcium and

phosphorous doses. Limitations to venous access, however, may preclude the

infusion of concentrated calcium solutions peripherally, and the patient’s end organs

may be resistant to vitamin D. Thus, metabolic bone disease is not unexpected in a

premature infant such as J.H.

Aluminum, a contaminant in some parenteral salt products (particularly calcium),

also may play a role in impaired bone mineraliziation.

41 Low serum phosphorus with

high alkaline phosphatase, undermineralized bones, and fractures resulting from

routine handling are consistent with a diagnosis of rickets.

Parenteral nutrition solutions provide calcium and phosphorus in much smaller

amounts than the infant would accumulate in utero.

42 Solution pH, temperature,

calcium salt, and final calcium and phosphorus concentrations influence their

solubility in PN solutions. An acidic PN solution favors the solubility of these salts.

The pH of commercially available amino acid preparations ranges from 5.4 in

PAAFs to 7 in adult amino acid formulations. The addition of L-cysteine, with a pH

of 1.5, also makes the solution more acidic. Because dextrose also is acidic,

solutions with higher dextrose concentrations are more acidic. Of note, colder

storage temperatures promote calcium and phosphorus solubility. Therefore,

refrigerated PN solutions may appear to be free of precipitate on visual inspection.

Calcium and phosphate can precipitate, however, when warmed to room temperature,

or when infused into patients with fever or in incubators. Calcium salt selection is

another important consideration because the chloride salt dissociates rapidly and

favors precipitation, whereas the gluconate and gluceptate salts dissociate less

quickly.

Serum phosphorus concentrations should be monitored several times per week and

phosphorus intake adjusted to prevent symptomatic hypophosphatemia. Serum

calcium is not useful as an indicator of disease activity because it will remain normal

at the expense of bone mineralization. This is demonstrated by J.H.’s serum calcium

at the time of diagnosis.

Parenteral Nutrition-associated Liver Disease

CASE 103-7, QUESTION 9: On the 56th day of life, J.H. is noted to be mildly jaundiced. A review of his

laboratory tests reveals the following:

Age (days)

Test 22 29 36 43 50

Aspartate aminotransferase (AST) (units/L) (normal,

<40)

14 17 15 20 25

Alanine aminotransferase (ALT) (units/L) (normal,

<28)

6 7 10 10 11

Alkaline phosphatase (international units/L) (normal,

<350)

103 158 345 506 695

Bilirubin

Indirect (normal, <1 mg/dL) 0.9 0.9 0.8 0.8 0.9

Direct (normal, <0.2 mg/dL) 0.1 0.1 0.8 1.6 3

Could this be related to his PN?

Parenteral nutrition-associated liver disease (PNALD) is severe liver disease due

to extended parenteral feeding, which can cause permanent damage and even liver

failure. In past decades, hepatic damage has been reported in up to one-half of infants

receiving PN,

43 with a higher prevalence (up to 50%) in VLBW infants such as J.H.

Although it is still a concern today, PNALD is less prevalent because of a better

understanding of how to treat infants requiring long-term PN. The laboratory

abnormalities reported in J.H. are typical of this complication. The first change

observed is usually an elevated direct (conjugated) bilirubin, which can occur as

early as 2 weeks after beginning PN. Increases in the

p. 2151

p. 2152

serum concentrations of the hepatic enzymes, AST and ALT, lag 2 weeks or more

behind the rise in direct bilirubin. Alkaline phosphatase also can rise, but it is a

nonspecific indicator of liver disease. Alkaline phosphatase is produced by the liver,

GI tract, and bones. Although the laboratory results observed in J.H. are consistent

with the pattern associated with PNALD, and many components of PN solutions have

been associated with the development of cholestasis, other potential causes also

exist.

43 PNALD is a diagnosis of exclusion; therefore, other causes, such as viral

hepatitis, must be ruled out.

J.H. has several other risk factors for developing cholestasis, and prolonged

enteral fasting may be the most significant.

43 Stimulation of bile flow and gallbladder

contraction depend on GI hormones, which depend on enteral feeding for their

release.

43 Absence of these hormones, therefore, can promote cholestasis.

43

Immature

hepatic function secondary to prematurity also places J.H. at risk, as does the

duration of PN therapy. As the duration of PN use increases, so does the prevalence

of hepatic disease in premature infants; 25% of infants nourished in this manner for

30 days or more show evidence of cholestasis.

43 Surgical patients have a greater

likelihood of developing hyperbilirubinemia than medical patients, especially those

requiring GI surgery.

43 Many surgical procedures are associated with a higher risk of

jaundice.

43 Finally, J.H.’s infection increases his risk for cholestasis.

43

The use of adult amino acid preparations in infants increases the risk of

cholestasis. In one study, the incidence of cholestasis in VLBW infants receiving

TrophAmine was reduced to 23% relative to historical controls of 30% to 50%.

44

In

another study comparing the two PAAFs mentioned above, 33% of infants receiving

Aminosyn PF developed cholestasis as compared with 13% of infants who received

TrophAmine.

45 An additional risk factor for cholestasis not present in J.H. is the

administration of large amounts of protein or dextrose. Because amino acids are

actively transported in hepatocytes, it is important to provide appropriate types and

amounts of amino acids to minimize the development of cholestasis. In one study, a

high-protein regimen (3.6 g/kg/day) was associated with an earlier onset and greater

degree of cholestasis than a low-protein regimen (2.3 g/kg/day).

46 Similarly, dextrose

overload is also a known cause of hepatic steatosis. Therefore, overly aggressive

feeding of J.H. with PN should be avoided.

In addition to the hepatic damage, gallstones have been reported in infants and

children receiving PN.

43 The ileal resection performed during the acute phase of his

necrotizing enterocolitis may put J.H. at increased risk for this hepatobiliary

complication as well.

CASE 103-7, QUESTION 10: What modifications to J.H.’s PN regimen should be made in the presence of

cholestasis?

First, the institution of enteral feeding must be considered. Even low-volume

trophic feeding may help alleviate the condition and should be attempted in

cholestatic patients. Next, the protein and glucose dose provided by the PN should be

evaluated. During cholestasis, calories should be provided using an appropriate mix

of protein, carbohydrate, and fat.

Although the effect of cycling a patient off PN has not been evaluated in clinical

trials, this should be considered. Cycling PN, in which the infusion rate is gradually

decreased to off for a period and then restarted and gradually increased to the

desired rate, will decrease the length of time the liver is exposed to PN. VLBW

infants, however, may become hypoglycemic even with very gradual decreases in

infusion rate, so this option should be used with care. In any event, a short time off

PN (e.g., 2 hours) should be attempted.

The trace elements provided by the formulation should be examined. Both copper

and manganese are enterohepatically recycled and may accumulate in liver disease.

Manganese can also contribute to hepatotoxicity and should be removed from J.H.’s

PN solutions. Studies have not established when removal of copper and manganese is

warranted. The inappropriate removal of copper could lead to anemia, osteopenia,

and neutropenia. Therefore, decreasing the copper dose and monitoring serum

concentrations of both copper and manganese should guide therapy.

Current studies have demonstrated that using omega-3 long-chain fatty acids,

derived from fish oil, can reverse the liver damage caused by PNALD. Fish oil is

high in eicosapentaenoic and docosahexaenoic acids, which do not impair bile flow

and may actually diminish fat accumulation in the liver. Omegaven, the parenteral

fish oil-based intravenous fat emulsion, is being used under the compassionate use

protocol and not currently approved by the FDA.

47 Other research is being done using

an oral formulation of fish oil in infants as a supplement to reverse PNALD.

48

Pharmacologic interventions have had limited success in the management of

PNALD. Phenobarbital has not been shown to be effective in reducing or reversing

it.

49 Ursodiol 10 to 20 mg/kg/day has been used successfully in the treatment of other

cholestatic liver diseases, and preliminary reports indicate that it may also improve

PNALD in children.

50 Ursodiol, a naturally occurring nontoxic bile acid, presumably

works by displacing and replacing the endogenously produced, potentially toxic bile

salts that accumulate with cholestasis.

The antibiotic metronidazole also appears promising in the prevention of PNALD

in adults. Metronidazole inhibits the bacterial overgrowth in the GI tract that occurs

with intestinal stasis. The bacteria are responsible for increased formation of

hepatotoxic bile acids such as lithocholate; 25 mg/kg/day of metronidazole has been

shown to be effective.

51

CASE 103-7, QUESTION 11: Project the course of J.H.’s liver disease if PN is discontinued and enteral

feedings are instituted within 2 weeks. What may occur if enteral feedings cannot be instituted?

It is difficult to predict a successful wean from PN. Historically, success has been

associated with longer length of intact small intestine. Additionally, studies in

children with short bowel syndrome have shown that serum citrulline levels may

predict the ability to successfully wean a patient from PN. Citrulline is a free amino

acid that is produced by the small bowel enterocytes. Therefore, it may be warranted

to measure J.H.’s serum citrulline level before weaning from PN.

52

If PN can be discontinued soon after the onset of cholestasis, the prospects for J.H.

to recover normal hepatic function are good. Jaundice usually resolves within 2

weeks after PN is discontinued, and the biochemical abnormalities normalize soon

thereafter.

43 The pathologic changes observed on biopsy resolve even more slowly.

Biopsy evidence of cholestasis has been observed for up to 40 weeks after resolution

of clinical and serologic evidence of hepatic disease.

43

If enteral feedings cannot be instituted successfully, the prognosis for J.H.’s liver

function is not as good. Studies have demonstrated that infants receiving PN for 90

days or more had biopsy evidence of irreversible liver damage.

43 Thus, it clearly is

advantageous to convert J.H.’s nutrition to the enteral route as soon as he tolerates

such a change.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

p. 2152

p. 2153

Key References

Greene HL et al. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants

and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral Nutrient

Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition

[published corrections appear in Am J Clin Nutr. 1989;49(6):1332; Am J Clin Nutr. 1989;50(3):560]. Am J Clin

Nutr. 1988;48(5):1324. (2)

Gura KM et al. Reversal of parenteral nutrition-associated liver disease in two infants with short-bowel syndrome

using parenteral fish oil: implications for future management. Pediatrics. 2006;118(1):e197. (47)

Hay WW Jr et al. Workshop summary: nutrition of the extremely low birth weight infant. Pediatrics.

1999;104(6):1360. (24)

Heird WC et al. Intravenous alimentation in pediatric patients. J Pediatr. 1972;80(3):351. (22)

Heird WC et al. Pediatric parenteral amino acid mixture in low birth weight infants. Pediatrics. 1988;81(1):41. (37)

Helms RA et al. Comparison of a pediatric versus standard amino acid formulation in preterm neonates requiring

parenteral nutrition. J Pediatr. 1987;110(3):466. (38)

Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957;19(5):823.

(1)

Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006;130(2, suppl

1):S70. (43)

King C et al; Centers for Disease Control and Prevention. Managing acute gastroenteritis among children oral

rehydration, maintenance, and nutritional therapy. MMWR Recomm Rep. 2003;52(RR-16):1. (4)

Tillman EM et al. Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with

short-bowelsyndrome. Pharmacotherapy. 2011;31(5):503–509. (48)

Wessel JJ. Human milk. In: Corkins MR, ed. The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum. Silver

Spring, MD: American Society for Parenteral and Enteral Nutrition; 2010:120. (8)

Key Websites

American Society for Parenteral and Enteral Nutrition. Clinical guidelines

http://www.nutritioncare.org/guidelines_and_clinical_resources/. Accessed July 16, 2017.

Journal of Parenteral and Enteral Nutrition. Guidelines for the use of parenteral and enteral nutrition in adult and

pediatric patients. http://pen.sagepub.com/content/26/1_suppl/1SA.refs. Accessed September 15, 2015.

COMPLETE REFERENCES CHAPTER 103 PEDIATRIC

FLUID, ELECTROLYTES, AND NUTRITION

Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957;19(5):823.

Greene HL et al. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants

and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral Nutrient

Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition

[published corrections appear in Am J Clin Nutr. 1989;49(6):1332; Am J Clin Nutr. 1989;50(3):560]. Am J Clin

Nutr. 1988;48(5):1324.

US Centers for Disease Control and Prevention. 2000 CDC growth charts: United States.

http://www.cdc.gov/nchs/data/series/sr_11/sr11_246.pdf. Accessed October 1, 2010.

King C et al. Centers for Disease Control and Prevention. Managing acute gastroenteritis among children oral

rehydration, maintenance, and nutritional therapy. MMWR Recomm Rep. 2003;52(RR-16):1.

Gidding SS et al. American Heart Association. Dietary recommendations for children and adolescents: a guide for

practitioners. Pediatrics. 2006;117(2):544.

Drozdowski LA et al. Ontogeny, growth and development of the small intestine: understanding pediatric

gastroenterology. World J Gastroenterol. 2010;16(7):787.

Gartner LM et al. American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of

human milk. Pediatrics. 2005;115(2):496.

WesselJJ. Human milk. In: Corkins MR, ed. The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum. Silver

Spring, MD: American Society for Parenteral and Enteral Nutrition; 2010:120.

Helms RA et al. Protein digestion, absorption, and metabolism. In: Corkins MR, ed. The A.S.P.E.N. Pediatric

Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition;

2010:31.

Oski FA. Iron deficiency—facts and fallacies. Pediatr Clin North Am. 1985;32(2):493.

Wagner C, Greer FR; American Academy of Pediatrics Section on Breastfeeding; American Academy of

Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and

adolescents. Pediatrics. 2008;122(5):1142.

American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the

newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1):297.

Bhatia J, Greer F. American Academy of Pediatrics Committee on Nutrition. Use of soy protein-based formulas

in infant feeding. Pediatrics. 2008;121(5):1062.

Greer F et al. American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics

Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic

disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of

complementary foods, and hydrolyzed formulas. Pediatrics. 2008;121(1):183.

Centers for Disease Control and Prevention (CDC). Enterobacter sakazakii infections associated with the use of

powdered infant formula—Tennessee 2001. MMWR Morb Mortal Wkly Rep. 2002;51(14):298.

Fomon SJ et al. Cow milk feeding in infancy: gastrointestinal blood loss and iron nutritional status. J Pediatr.

1981;98(4):540.

Low LC. Inborn errors of metabolism: clinical approach and management. Hong Kong Med J. 1996;2(3):274.

McClure RJ. Trophic feeding of the preterm infant. Acta Paediatr Suppl. 2001;90(436):19.

Mehta NM, Duggan CP. Nutritional deficiencies during critical illness. Pediatr Clin North Am. 2009;56(5):1143.

Yehuda S et al. Nutritional deficiencies in learning and cognition. J Pediatr Gastroenterol Nutr. 2006;43(Suppl

3):S22.

Hill R et al. An evaluation of D-xylose absorption measurements in children suspected of having small intestinal

disease. J Pediatr. 1981;99(2):245.

Heird WC et al. Intravenous alimentation in pediatric patients. J Pediatr. 1972;80(3):351.

Thureen PJ et al. Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition. Am

J Clin Nutr. 1998;68(5):1128.

Hay WW Jr et al. Workshop summary: nutrition of the extremely low birth weight infant. Pediatrics.

1999;104(6):1360.

te Braake FW et al. Amino acid administration to premature infants directly after birth. J Pediatr.

2005;147(4):457.

Patole S. Strategies for prevention of feed intolerance in preterm neonates: a systematic review. J Matern Fetal

Neonatal Med. 2005;18(1):67.

Kao LC et al. Triglycerides, free fatty acids, free fatty acids/albumin molar ratio and cholesterol levels in serum

of neonates receiving long-term lipid infusions: controlled trial of continuous and intermittent regimens. J Pediatr.

1984;104(3):429.

Bell MJ et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg.

1978;187(1):1.

Pietz J et al. Prevention of necrotizing enterocolitis in preterm infants: a 20-year experience. Pediatrics.

2007;119(1):e164.

Cury-Boaventura MF et al. Toxicity of soybean oil emulsion on human lymphocytes and neutrophils. JPEN J

Parenter Enteral Nutr. 2006;30(2):115.

Andrew G et al. Lipid metabolism in the neonate: II. The effect of Intralipid in bilirubin binding in vitro and in vivo.

J Pediatr. 1976;88(2):279.

Weber SS et al. Availability of insulin from parenteral nutrient solutions. Am J Hosp Pharm. 1977;34(4):353.

Sajbel TA et al. Use of separate insulin infusions with total parenteral nutrition. JPEN J Parenter Enteral Nutr.

1987;11(1):97.

Yeh TF et al. Metabolic rate and energy balance in infants with bronchopulmonary dysplasia. J Pediatr.

1989;114(3):448.

Kurzner SI et al. Growth failure in infants with bronchopulmonary dysplasia: nutrition and elevated resting

metabolic expenditure. Pediatrics. 1988;81(3):379.

Covelli HD et al. Respiratory failure precipitated by high carbohydrate loads. Ann Intern Med. 1981;95(5):579.

Heird WC. Pediatric parenteral amino acid mixture in low birth weight infants. Pediatrics. 1988;81(1):41.

Helms RA et al. Comparison of a pediatric versus standard amino acid formulation in preterm neonates requiring

parenteral nutrition. J Pediatr. 1987;110(3):466.

Adamkin D et al. Comparison of two neonatal intravenous amino acid formulations in preterm infants: a

multicenter study. J Perinatol. 1991;11(4):375.

Crill CM et al. Carnitine: a conditionally essential nutrient in the neonatal population? J Pediatr Pharm Pract.

1999;4(3):127.

Poole RL et al. Aluminum content of parenteral nutrition in neonates measured versus calculated levels. J Ped

Gastroenterol Nutr. 2010;50(2):208.

Ziegler EE et al. Body composition of the reference fetus. Growth. 1976;40(4):329.

Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006;130(2,

Suppl 1):S70.

Mauer EC, Penn D. Incidence of cholestasis in low birth weight (LBW) neonates on TrophAmine [abstract].

JPEN J Parenter Enteral Nutr. 1991;15(1, Suppl):25S.

Wright K et al. Increased incidence of parenteral nutrition associated cholestasis with aminosyn PF compared to

trophamine. J Perinatol. 2003;23(6):444.

Vileisis RA et al. Prospective controlled study of parenteral nutrition-associated cholestatic jaundice: effect of

protein intake. J Pediatr. 1980;96(5):893.

Gura KM et al. Reversal of parenteral nutrition-associated liver disease in two infants with short-bowelsyndrome

using parenteral fish oil: implications for future management. Pediatrics. 2006;118(1):e197.

Tillman EM, et al. Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with

short-bowelsyndrome. Pharmacotherapy. 2011;31(5):503–509.

Gleghorn EE et al. Phenobarbital does not prevent total parenteral nutrition-associated cholestasis in non-infected

neonates. JPEN J Parenter Enteral Nutr. 1986;10(3):282.

San Luis VA, Btaiche IF. Ursodiol in patients with parenteral nutrition-associated cholestasis. Ann Pharmacother.

2007;41(11):1867.

Günsar C et al. The biochemical and histopathological effects of ursodeoxycholic acid and metronidazole on total

parenteral nutrition-associated hepatic dysfunction: an experimental study. Hepatogastroenterology.

2002;49(44):497.

Fitzgibbons S et al. Relationship between serum citrulline levels and progression to parenteral nutrition

independence in children with short bowelsyndrome. J Pediatr Surg. 2009;44(5):928.

p. 2153

Medication administration to children can be challenging. For oral

administration, dosing syringes or droppers should be used rather than

household spoons or cups. The administration of medications by any

route may require special techniques in an uncooperative child.

Case 104-1 (Question 1)

Diaper dermatitis presents as a mild red rash that often progresses to

increased redness and lesions outside the diaper area. Barrier creams

are recommended for initial treatment with the addition of a topical

antifungal for dermatitis lasting longer than 3 days and spreading outside

the diaper area.

Case 104-2 (Questions 1, 2)

Fever in children may be the result of a common viral infection, but could

also be an indicator of a more serious bacterial infection or lead to

complications such as febrile seizures. Proper management depends in

large part on accurate assessment.

Case 104-3 (Questions 1, 2)

The treatment of cough and cold symptoms in children younger than 6

years of age is generally supportive with nasalsaline, hydration, and

humidification. Over-the-counter agents have little proven effectiveness

and have been associated with severe adverse effects owing to

inadvertent overdoses during parental administration.

Case 104-4 (Question 1)

Constipation can be defined by a delay or difficulty in stooling for at least

2 weeks duration. Constipation is most commonly functional, and may

be managed with behavioral modification or drug therapy.

Case 104-5 (Question 1)

Gastroenteritis, although usually self-limiting, may result in clinically

significant dehydration in infants and children. Assessment of the

degree of dehydration is important in determining whether oral

rehydration is appropriate or hospital admission with intravenous

rehydration is required.

Case 104-6 (Questions 1–3)

Gastroesophageal reflux is a common disorder in young infants. Most

will require no intervention. Some, however, will require feeding

modifications and possibly drug therapy, including acid-suppressing or

prokinetic agents.

Case 104-7 (Questions 1, 2)