Nutrient Metabolism
and Nutrition Therapy During
Critical Illness
Nilesh M. Mehta
PEARLS
Accurate assessment of nutritional status and provision of individually
tailored optimal nutrition to the critically ill child
are important but elusive goalS of pediatric critical care.
 Malnutrition is associated with increased physiologic instability
and the need for increased quantity of care in the ICU.
Careful assessment of nutritional status on admission to the
PICU .allOwS identification of at-risk drynainourished children.
The hyperrnetabolic stress response places variable energy.
 demands On the critically ill,child that must: be met With. •
evidence-based strategies. The metabolic response to critical
illness results in glucose and lipid intolerance and increased
protei i in i are often incurred due to the burden of illness or suboptimal
n breakdown, resultng n weight reducton and loss of
. nutritient intake and may result in poor outcomes. Safe provi-
lean body mass...
 Supply of adequate glucose and protein does not reduce protein
breakdown and nitrogen loss during the:metabolic stress
response.:HoweVer, protein balance may be.improved by
increaseciprotein.synthesis in: the presence of relentless protein
Catabolism. In starvation, protein catabolism can be reversed
• if adequate energy intake is provided.'This characteristic.
differentiates starvation from a hypermetabolit state.,
• has long been recognized as a problem, a significant propor-
. •
Failure to accurately estimate or measure energy eXpenditure during
critical illness results in both underfeeding and •
overfeeding, with:significant and unintended energy
imbalances over the Cdurse of ilineSs: Indirect Calorime
targeted at high-risk patients helps prevent energy
imbalancet in the PICU.
 Early enteral nutrition (EN) in patients with a
functioning gaStrointestinal tract is desirable. It has been
shown to decrease infectious episodes and decrease length of
hoSpital stay in critically ill patients.
 The......................gastric.route is preferred for enteral nutrition. PoStpyloric
(small bowel) feeding May, be` considered inpatients at risk of
. aspiration orwhen gastriC feeding.has not been tolerated.
... .•
 A significant number of patients experience interruptions.to EN
during their PICU course. Fluid restriction, prolonged fasting for
PrOcedures, feeding tube blockage or dislocation, perceived
 feed intolerance (due to abdominal disteriSion, discomfort, or
high gastric residual volumes); vomiting, diarrhea, and overall
failure to prioritize nutritional support in the PICU'are some of
the factors that Make EN challenging at the bedside.
,
 Although widespread in its application, parenteral.nutritiOn
is assOCiated:with MechanicatinfectiouS, and metabolic
complications and hence should be used only in carefully
selected patients where EN is contraindicated, nottblerated,
or has failed toprpvide adequate nutrition.
Malnutrition is prevalent in critically ill children at the time of
admission to the pediatric intensive care unit (PICU).1,2 Fur-
ther nutritional deficiencies during the course of their illness
sion of optimal nutrients during hospitalization is an impor-
tant goal of pediatric critical care. The changing metabolic
state during the course of critical ilness results in unpredict-
able energy demands that need to be carefully matched with
evidence-based nutritional strategies. However, prediction,
estimation, and measurement of true energy expenditure in
PICU patients can be challenging. Failure to accurately esti-
mate or measure energy expenditure can potentially result in
unintended underfeeding or overfeeding. While underfeeding
tion of critically ill children are at the risk of being overfed.3
Furthermore, there exist a myriad of barriers that impede the
delivery of prescribed nutrients to the critically ill child and
result in a delay or a failure to achieve the prescribed energy
goal. The complexiti6 of critical care or the nature of illness
frequently conflict with nutrient provision. However, many
barriers to bedside nutrient delivery may be avoidable. Exami-
nation of existing literature, audits of bedside practice, and
multidisciplinary collaborations have helped identify optimal
nutritional strategies, illuminated areas of practice deficien-
cies or knowledge gaps, and highlighted future priorities for
research. There has been a resurgence in awareness and an
increase in our understanding of the role of nutrition therapy
during pediatric critical illness. However, the perceived ben-
efits of novel therapies such as immunonutrition, tight glyce-
mic control, and hormonal modulation of the stress response
have not yet been realized in the general PICU population.
Future studies will darify the role of these strategies in improv-
ing patient outcomes in the PICU. Until then, careful screen-
ing for malnutrition, awareness of the metabolic state during
1073
1074 Section V — Renal, Endocrine, and Gastrointestinal Systems
the course of illness, accurate assessment of energy demands
with attention to energy balance, multidisciplinary efforts to
overcome common barriers to nutrient intake at the bedside,
and a commitment to prioritizing nutritional support during
critical illness are necessary to meet nutritional goals.
alnutritis , the Critically
Ell Pediatric Patient
Critical illness increases metabolic demand on the host in the
early stages of the stress response, when nutrient intake may
be limited. Asa result, children admitted to the PICU are at
risk of deteriorating nutritional status and anthropometric
changes-with-in-creased-morbidity.-1—This-effeLt is-more-pro-
nounced in a subgroup of patients who are already malnour-
ished or at risk of malnutrition on admission. The prevalence
of malnutrition in children admitted to the ICU has remained
largely unchanged over the last two decades. One in every four
children admitted to the PICU shows signs of acute and/or
chronic malnutrition on admission.1'2 A majority of PICU
patients present with conditions that impede normal growth.
Nutritional status affects physiologic responses and influences
outcome. Malnutrition is associated with increased physi-
ologic instability and the need for increased quantity of care
in the ICU.4 Despite its high prevalence and consequences,
medical awareness of malnutrition is lacking. The nutritional
status of hospitalized patients is not routinely assessed, and
only a minority of patients are referred for expert nutritional
consultation or supports Careful nutritional evaluation at
admission to the PICU will allow identification of children at
risk for further nutritional deterioration and, hence, candi-
dates for interventions to optimize nutrient intake.
Assessment of Nutritional
Status
Assessment of the nutritional status in the critically ill child
is vital but often challenging. Clinicians use a combination of
anthropometric and laboratory data to diagnose undernour-
ishment. Carefully elicited past history with details of weight
gain, dietary history, recent illness, and medications allows
identification of risk factors for preoperative malnutrition.
Weight on admission to the hospital is important and may be
the only measure of the actual-dry weight before_capillary leak
syndrome results in edema and weight gain. Unless regular and
accurate weights are obtained, acute changes in nutritional sta-
tus may be missed or detected late.6 Children in the PICU are
often not weighed as the procedure is deemed to be unsafe or
not important. The lack of availability of reliable weight
trends in PICU patients reflects the overall low priority among
health care workers for nutrition-al assessment and, as a result, the
true incidence of malnutrition in this-cohort may indeed be
underestimated. Physical examination should be directed
toward specific signs of nutritional and metabolic deficiencies.
Hair, skin, eyes, mouth, and extremities may reveal stigmata of
protein-energy malnutrition or vitamin and mineral
deficiencies.
A variety of other measurements including arm anthropom-
etry (mid-upper arm circumference and triceps skin fold),
body kngth, and-body mass index-have been-used-to-monitor
growth in children. In a study of infants and children admitted
to the PICU, significant anthropometric abnormalities were
detected by changes in mid-arm circumference and weight
in correlation with energy deficits.1 These anthropometric
abnormalities accrued during the PICU admission returned
to normal by 6 months after aildiarge. Using reproducible
anthropometric measures, other investigators detected malnu-
trition in a majority of children on admission to their PICU.?
Children with malnutrition had increased mortality compared
with those without malnutrition.7 On follow-up, a significant
portion of children with malnutrition had further -deteriora-
tion in nutritional status. Although bedside anthropometric
methods are inexpensive, they are sporadically applied in hos-
pitalized children, may be insensitive in the setting of critical
illness, and are limited by significant interobserver variability.
Weight changes and other anthropometric measurements in
critically-ill children-should-be-interpreted in the-context of
edema, fluid therapy, volume overload, and diuresis. In the
presence of ascites or edema, ongoing loss of lean body mass
may not be evident using weight monitoring alone.
Body Composition
Body composition is emerging as a primary determinant of
health and a predictor of morbidity and mortality in children.
Preservation and accrual of lean body mass during illness are
important predictors of clinical outcomes in patients with
sepsis, cystic fibrosis, and malnutrition.8'9 Body composition
is measured by a variety of techniques including body densi-
tometry by underwater weighing, neutron activation analysis,
total-body potassium determination, bioelectrical imped-
ance assessment (BIA), and dual-energy x-ray absorptiometry
(DXA). Most of these methods are not practical for applica-
tion in the clinical management of a critically ill child. DXA
is a radiographic technique that can determine the
composition and density of different body compartments (fat,
lean tissue, fat-free mass, and bone mineral content) and
their distribution in the body. DXA has been used extensively
in pediatric practice for determining fat-free mass, fat mass, and
lean mass, and it is recognized as a reference method for body
composition research.1° Its results correlate well with direct
chemical analyses, and there is good agreement between
percentage body fat estimated by hydrodensitometry and
DXA.11 However, DXA is not practical for application in the
PICU. BIA, in contrast, is a bedside technique that can be
applied to pediatric patients without exposure to radiation and
with ease.12,13 Electrical current is conducted by body_ water
and isimpeded by other body components. BIA estimates
the volumes of body compartments, including extracellular
water and total body water (TBW). TBW measures can be
used to estimate lean body mass by applying age-appropriate
hydration factors. BIA has not been validated in critically ill
populations; hence, its use outside clinical studies is not
recommended in the PICU. The ideal bedside body
composition measurement technique in critically ill patients
remains elusive.
Biochemical Assessment
The nutritional status can also be assessed by measuring the
visceral (or constitutive) protein pool, the acute-phase protein
pool, nitrogen balance, and resting energy expenditure (REE).
Visceral-proteins are xapid-tumover proteins-produced-in the
liver. Low circulating levels of visceral protein are seen in the
setting of malnutrition, inflammatory states, and impaired
hepatic synthetic filmdom The reliability of serum albumin as
 Chapter 75 — Nutrient Metabolism and Nutrition Therapy During Critical Illness 1075
a marker of visceral protein status is questionable. Albumin has
a large pool and a half-life of 14 to 20 days, and is not an indi-
cator of the immediate nutritional status. Serum albumin may
be affected by changes in fluid status, albumin infusion, sepsis,
trauma, and liver disease, and these changes are independent of
nutritional status. Prealbumin (also known as transthyretin or
thyroxine-binding prealbumin) is a stable circulating glycopro-
tein synthesized in the liver. It binds with retinol-binding pro-
tein and is involved in the transport of thyroxine and retinol.
Prealbumin, so named by its proximity to albumin on an elec-
trophoretic strip, is readily measured in most hospitals and is a
good marker for the visceral protein poo1.14,13 It has a half-life
of 24 to 48 hours and reflects more acute nutritional changes.
Prealbumin concentration is diminished in liver disease. Acute-
phase reactant proteins are elevated proportional to the sever-
ity of injury in response to cytokines released during stress
response and have been used to longitudinally monitor the
inflammatory response. Serum levels of acute-phase protein are
elevated in children within 12 to 24 hours after burn injury, due
to hepatic reprioritization of protein synthesis.16 When mea-
sured serially, serum prealbumin and C-reactive protein (CRP)
are inversely related (i.e., serum prealbumin levels decrease
and CRP levels increase, with the magnitude proportional to
injury severity, and then return to normal as the acute injury
response resolves). In infants after surgery, decreases in serum
CRP values to less than 2 mg/dL have been associated with the
return of anabolic metabolism and are followed by increases
in serum prealbumin levels.17 Proinflammatory cytokines such
as interleukin 6 (IL-6) are recognized as early markers of the
systemic inflammatory response syndrome (SIRS) in several
disease models. Serum concentrations of IL-6 may be useful in
identifying patients at risk for nutritional deterioration and to
determine whether the inflammatory response is intact.
Chemistry profiles should be monitored on admission and
repeated periodically. Serum electrolytes, blood urea nitrogen,
glucose, coagulation profile, iron, magnesium, calcium, and
phosphate levels are routinely monitored. Adequacy of cel-
lular immunity can be estimated through the measurement
of total lymphocyte count and by delayed-type hypersensitiv-
ity testing with a series of common antigens (e.g., Candida,
Trichophyton, tuberculin).
Mutritional Requirements
During Critica/ fitness
Metabolic Consequences of the Stress
Response
The energy burden imposed by the metabolic response to
injury, surgery, or inflammation may be proportional to the
severity and duration of the stress, but cannot always be accu-
rately estimated and varies in intensity and duration between
individuals.
Importantly, nutritional support itself cannot reverse or
prevent the metabolic stress response. Failure to provide opti-
mal calories and protein during the acute stage of illness can
result in an exaggeration of existing nutritional deficiencies
or further exacerbate an underlying poor nutritional status.
Respiratory compromise involving loss of respiratory muscle
mass, cardiac dysfunction and arrhythmias involving loss of
myocardial muscle tissue, and intestinal dysfunction involv-
ing loss of the gut barrier contribute to the morbidity and
mortality of critical illness. In some cases, overestimation
of this energy cost of metabolic stress may result in provision
of energy in excess of requirement. Hence, large energy
imbalances attributable to underfeeding and overfeeding
in critically ill children must be avoided.3 This requires an
individualized nutritional regimen that must be tailored for
each child and reviewed regularly during the course of illness.
A basic understanding of the metabolic events that accompany
critical illness and surgery is essential for planning appropriate
nutritional support in critically ill children.
The unique hormonal and cytokine profile manifested dur-
ing critical illness is characterized by an elevation in serum
levels of insulin, glucagon, cortisol, catecholamines, and pro-
inflammatory cytokines." Increased serum counterregulatory
hormone concentrations induce insulin and growth hormone
resistance, resulting in the catabolism of endogenous stores of
protein, carbohydrate, and fat to provide essential substrate
intermediates and energy necessary to support maintenance
energy and micronutrient needs in addition to the ongoing
metabolic stress response. Figure 75-1 illustrates the basic
pathways involved in the metabolic stress response.
In general, the net increase in muscle protein degrada-
tion, characteristic of the metabolic stress response, results
in a large amount of free amino acids in the circulation. Free
amino acids are used as the building blocks for the rapid syn-
thesis of proteins that act as inflammatory response mediators
and are used for tissue repair. Protein breakdown may con-
tinue for an extended period of time, in an attempt to channel
the amino acids through the liver, wherein their carbon skel-
etons are used to create glucose through gluconeogenesis and
for production of glucose as the preferred energy substrate
for the brain, erythrocytes, and renal medulla. Reprioritiza-
tion of protein during the metabolic stress results in increased
synthesis of acute-phase reactant proteins such as C-reactive
protein, a racid glycoprotein, haptoglobin, a l- antitrypsin,
a2-macroglobulin, ceruloplasmin, and fibrinogen. Plasma
concentrations of other proteins, including transferrin and
albumin, decrease with injury or sepsis. Overall intense pro-
tein catabolism outstrips anabolism with a net negative pro-
tein balance. This condition results in weight reduction and
rapid loss of lean body mass. The intense catabolism seen in
metabolic stress cannot be suppressed by supplying calories,
and negative protein balance continues relentlessly. This is
one of the principal differences between stress response and
starvation. Starvation, or protein-calorie malnutrition, may
be caused by socioeconomic, psychosocial, disease-related,
or iatrogenic factors. The metabolic response to starvation
involves decreased secretion of insulin and thyroid hormones,
normal secretion of glucocorticoids and catecholamines, and
decreased oxygen consumption. In starvation states, the body
tries to preserve itself by using less energy for basic metabolic
functions; thus, overall metabolic rate decreases. Metabolism
shifts to use fat as a primary energy source, and the corre-
sponding ketones help provide fuel for the brain and spare
glucose and protein utilization. However, body tissues still
must be broken down to supply amino acids for other criti-
cal functions, eventually leading to loss of lean body mass and
vital organ wasting, and possibly death. Although, provision
of additional proteins does not suppress protein catabolism,
it may decrease the negative protein balance by increasing
protein synthesis. Table 75-1 summarizes the basic differences
between starvation and metabolic stress.
1076 Section V — Renal, Endocrine, and Gastrointestin al Systems

KETONES TISSUE REPAIR

WOUND HEALING
Fuel for brain
Acute inflammatory
Lipolysis proteins
Fatty acids
Trauma N4.

Sepsis
Critical
illness

Urea

Glycolysis
Utilization TT GLUCOSE Fuel for
brain,
RBC, and
kidneys
Hyperglycemia

Figure 75-1. The metabolic response to stress. (Modified from Mehta N, Jaksic T.' The critically ill child. in: Duggan C, Watkins JB, Walker WA, editors:
Nutrition in pediatrics, Hamilton, ON, 2008, BC Decker.)

BMR, Basal metabolic rate; UUN, urinary urea nitrogen; LBM, lean body mass. associated with stress response, the provision of dietary glucose
TabIe -1 Metabolic Stress vs. Starvation does not decrease fatty acid turnover in times of illness. The
increased demand for lipid use in the setting of limited lipid
Metabolic Stress Starvation
stores puts the metabolically stressed neonate or previously
BMR malnourished child at high risk for the development of essential
• Oxygen consumption fatty acid deficiency.21,22 Preterm infants are most at risk for
.0(02) developing essential fatty acid deficiency after a short period
Rrotein catabolism of a fat-free nutritional regimen 22,23 The beneficial effects of the
acute metabolic response to illness/injury must be considered in
UUN H.
relation to the harmful consequences of a persistently severe
Weight loss Rapid SIOVv catabolic response. Nutritional therapy should aim to support the
IBM loss Early Late metabolic changes occurring during the acute catabolic stage.
Response to caloric PrOtein catabolism 'Protein catabolism With resolution of a hypermetabolic stress response, an anabolic
intake -- continues.. phase typically follows, with increased release of GH and IGF- 1.
`Insulin; cortiSol, and Supply of adequate nutrition is essential for this recovery phase.
catecholarnines • In summary, the metabolic response to critical illness results in
Ketones glucose and lipid intolerance and increased protein
GiLicOneogenesis
breakdown.

Supply of adequate nutritional intake under these cir -

cumstances is challenging, and yet recovery of critically ill
patients depends on their ability to utilize energy substrates
and synthesize new proteins. Carbohydrate turnover is simul-
taneously increased during the metabolic response, with a
significant increase in glucose oxidation and gluconeogenesis.
The administration of exogenous glucose does not blunt the
elevated rates of gluconeogenesis, however, and net protein
catabolism continues unabated.° A combination of dietary
glucose and protein may improve protein balance during
critical illness, primarily by enhancing protein synthesis. The
stress response to injury stimulates lipolysis and increased
fates Offdtty acidoxidation.-2° Increasedlaroxidati-on reflects---
the premiere role of fatty acids as an energy source during
critical illness. Triglycerides in adipose tissue are then cleaved
by hormone-sensitive lipase into fatty acids and glycerol. Fatty
acids are oxidized in the liver for energy via the tricarboxylic
acid or Krebs cycle. As seen with the other catabolic changes
Underfeeding and Overfeeding in the
Pediatric Intensive Care Unit
Individual assessment of energy requirements and provision
of optimal nutritional support should be the standard of care.
Both underfeeding and overfeeding are prevalent in the PICU,
with resultant nutritional deficiencies that are associated with
complications.4'24 True energy expenditure during acute ill-
ness may not be easily predicted and several studies have docu-
mented discrepancies in measured versus equation-estimated
energy expenditure. 25-27 Children with severe burn injury
demonstrate extreme hypermetabolism in the early stages of
injurr-Stan-dard- -equations-have -been -shown—to-underestk- -
mate the measured REE in this population.28 Unless increased
energy requirements during the acute stage of such illnesses
are accurately measured and matched by adequate intake,
 Chapter 75 — Nutrient Metabolism and Nutrition Therapy During Critical Illness 1077
cumulative energy deficits will ensue with decrease in weight,
loss of critical lean body mass, and a worsening of existing
malnutrition. Physicians have reported significantly escalated
energy demands in a child with severe paroxysmal dysauto-
nomia associated with ischemic brain injury. Failure to esti-
mate this increased energy need resulted in underfeeding in
this patient with severe weight loss during the course of illness
in the PICU.6 A variety of barriers, both unavoidable as well
as some avoidable, exist that impede optimal nutrient delivery
at the bedside and contribute to the likelihood of underfeed-
ing in the PICU.29'3° In the setting of fluid shifts, edema, and
capillary leak in acute illness, some of these negative anthro-
pometric outcomes may not be detected by the existing crude
assessment techniques. Underfeeding during acute illness,
with cumulative negative energy balance, has been associated
with poor outcomes. in critically ill adults.31 However, energy
imbalance in of the PICU population may also present in the
form of cumulative energy excess due to unintended overfeed-
ing. Indeed overfeeding in the PICU may be an underrecog-
nized entity with a potential impact on patient outcomes.
Children do not predictably mount the characteris -
tic hypermetabolic stress response as is seen in adults. The
metabolic response to stress from injury, surgery, or illness
is variable and the degree of hypermetabolism is unpredict-
able and unlikely to be sustained during a prolonged course
in the PICU.32 Critically ill children cannot be presumed to
be hypermetabolic following acute illness or injury and energy
expenditure may actually be decreased in some groups of
patients.33'34 While a sustained increase in metabolism has
been reported for weeks after burn injury, REE peak returns to
baseline within 12 hours after some surgical procedures.35'36
Indeed children on extracorporeal life support or after sur-
gery have failed to show any significant hypermetabolism,
and measured energy expenditure is dose to resting energy
expenditure in these populations.37 Critically ill children who
are sedated and mechanically ventilated may have significant
reduction in actual total energy expenditure, due to multiple
factors. Decreased activity during illness, attenuation of insen-
sible fluid losses in the controlled PICU environment, and
transient absence of growth during the acute illness all keep
total REE close to the basal rate, even in critically ill children.
Historically, stress or activity correction factors have been tra-
ditionally factored into basal energy requirement estimates
to adjust for the nature of illness, its severity, and the activ-
ity level of hospitalized subjects 38'39 These patients may be at
a risk of overfeeding when estimates of energy requirements
are based on age-appropriate equations developed for healthy
children, and especially if stress factors are incorporated in an
attempt to account for the perceived hypermetabolic effects of
the illness. Indirect calorimetry testing to determine the true
metabolic state must be considered before incorporating stress
factor correction to energy estimates in critically ill children.
While the problems with underfeeding have been well docu-
mented, overfeeding too has deleterious consequences 24,4°
Overfeeding increases ventilatory work by increasing carbon
dioxide production and can potentially prolong the need for
mechanical ventilation. Overfeeding may also impair liver
function by inducing steatosis and cholestasis, and increase
the risk of infection secondary to hyperglycemia. There are no
data in general pediatric populations for the role of hypocalo-
ric feeding.° In general, the energy goals should be assessed
and reviewed regularly in critically ill children.
Table 75-2Recommended Energy and Protein
llowances During Critical Illness
Data from the Food and Nutrition Board, National Academy of Science, National
Research Council, ed 9, Washington, DC, 1980.
Assessing Energy Expenditure
in Critically Ill Patients
Although the Food Agricultural Organization and the World
Health Organization (WHO) have recommended that energy
requirements and dietary recommendations be based on mea-
surements of energy expenditure, the resources and expertise
for such measurements are not easily available in all units.
Current recommendations for nutritional requirements of
the critically ill child are derived from limited data, based on
studies in healthy children and based on limited methodologic
approaches. Table 75-2 summarizes recommended energy
and protein intake for critically ill children. Recommenda-
tions for pediatric nutritional requirements have traditionally
focused on the supply of nutrients for growth. The compo-
nents of total energy expenditure in children include (1) basal
metabolic rate (BMR) 70%, (2) diet-induced thermogenesis
(DIT) 10%, (3) energy expended during physical activity (PA)
20% and (4) energy expended for growth. The sum of these
components determines the energy requirement for an indi-
vidual. The traditional components of energy expenditure
in healthy children may not apply during critical illness (see
Table 75-3). Thus, prescribing optimal energy for the critically
ill child requires careful review of each component of total
energy expenditure.
Previous recommendations for energy requirements were
based on estimates of basal metabolic rate or REE derived by
either indirect calorimetry or standard equations. 34,42 Studies
examining the performance of estimated energy needs in
relation to measured REE in critically ill children are
small-sized prospective or retrospective cohort studies. REE
estimates have a large individual variability, and predictive
equations are unreliable, particularly in underweight, over-
weight, or critically ill children.27,43,44 Newer equations have
attempted to improve the prediction of REE in children by
accounting for weight-based groups or by including puber-
tal staging, with variable success.44,45 These equations have
not been satisfactorily validated in critically ill children.46
1078 Section V Renal, Endocrine, and Gastrointestinal Systems
—
Table 5— om orients of Energy Expendrture: orma Health.vs. Critical Illness
ormal Health
BMR (60%-70%) Energy needed for maintaining vital processes of
the body
Measured in a recumbent position, in a thermoneu-
tral environment after 12-18 hours fast, when the
individual-has-awakened before starting daily
activities
Not practical for bedside
Sleeping energy expenditure,
a component of BMR was
shown to be equal to. REE = 0.9
REE (50%:;60% Corresponds to lean body mass
DIT or TEF (10%) + 10%
Growth (var Usually measured instead of BMR REE is measured at
rest in a thermoneutral environment, after 8-12
PA hours fast and not immediately after awakening
(variable) Reflects the amount of energy needed for food
Stress digestion, absorption, and part of synthesis
Energy for growth may be higher is healthy infan <2
years and during catch-u0 growth
Depends on age, activity level Decreased in hospitalized
patients
REE + DIT + PA + Growth
BMR, Basal metaboic rate; REE, resting energy exenditure; DIT, diet-induced therrnogenesis; TEF, thermic effect of food; PA, physical activity.
The variability of the metabolic state may be responsible
for the failure of estimation equations in accurately predict-
ing the measured REE in critically ill children. The applica-
tion of stress factors might predispose some patients to the
risk of overfeeding. Hence, it might be prudent to refrain
from using these corrections in the absence of an accurate
measurement of REE. Application of hypocaloric feeding
has been recommended in critically ill adults.47 There is not
enough evidence to recommend its general use in critically
ill children.
Indirect Calorimetry
Historically, indirect calorimetry (IC) has been regarded as
the gold standard for accurate measurement of REE. Energy
expenditure is obtained by measuring the volume of oxygen
consumed (Vo 2) and the volume of CO 2 produced (Vco 2)
over a period of time.48 From this estimate the 24-hour energy
intake is derived. Measurements of Vo2 and Vco2 are used to
calculate REE using the modified Weir equation: REE = [Vo2
Critical Illness
Related to metabolic state
May be increased in conditions such as inf ammation,
fever, acute or chronic
disease (e.g., cardiac
•
Measuredby indirect calorimotry•with-steady-state
c o n d i t i o n s
Increased energy needs.follovving enteral feeding; .
return to baseline approximately >4 hours of feeding
pulmonary)
Related to lean body-mass
Probably halted?
Variable
Probably overestimated during critical illness
Probably close to REE in most critically ill children
Addition of stress factors may be necessary where
.
relevant
(3.941) + Vco2 (1.11)] x 1440. This technique has been vali-
dated in healthy children by using a whole-body chamber to
allow 24-hour measurement. For obvious reasons, the whole-
body chamber cannot be used in critically ill children.
The application of IC in different PICU populations has
shown the variability in energy expended during illness. Weekes
and-Elia -showed a relatively higher resting metabolic rate in
critically ill children (37% higher than the resting metabolic
rate of age-matched healthy controls).49 However, the total
energy expenditure was reduced in a group of head-injured
children receiving enteral nutrition. Energy expenditure was
noted to decrease over time and returned to normal after the
second week of injury. In critically ill mechanically ventilated
children, use of sedation and muscle paralysis decreases the
component of energy requirement related to physical activ-
ity,5° and caloric needs in the critically ill child may_be lower
than previously considered. IC continues to be only sporadi-
cally applied in critically ill children, despite mounting evi-
dence of the inaccuracy of estimated basal metabolic rate
using standard equations. This could potentially subject a
subgroup of children in the PICU to the risk of underfeeding
or overfeeding. However, IC application is note feasible in all
patients due to (1) specific subject requirements, (2) device
limitations, and (3) need for expertise and resources. Table
75-4 describes some of the common problems associated with
IC testing in critically ill children. In the era of resource con-
straints, IC may be applied or targeted for certain high-risk
groups in the PICU.3 Selective application of IC may allow
many units to balance the need for accurate REE measure-
ment and limited resources (see Box 75-1 for suggested cri-
teria for targeted IC).5' While IC application has illuminated
our understanding of energy expended during critical illness,
this has yet to be translated into improving patient outcomes.
Studies examining the role of simplified IC technique, its
role in optimizing nutrient intake, its ability to prevent
overfeeding or underfeeding in selected subjects, and the cost-
benefit analyses °fits application in the PICU-aredesirable.-
The effect of energy intake on outcomes needs to be
examined in pediatric populations, especially in those on the
extremes of body mass index (BMI).
 Chapter 75 --Nutrient Metabolism and Nutrition Therapy During Critical Illness 1079

has advantages in children because of its noninvasive nature.

Table 75 4 Factors Associated
-
However, isotope decay is measured over two half-lives of the
nacCurate or Unreliable Indirect Calonme isotope, and hence the technique only gives an average estimate
eas Urements of total energy expenditure over a period of a few days. Ana-
lytical errors in the mass spectrometric estimation of isotope
Limitation's cr.,. enrichment, isotope fractionation during CO2 formation or
Error in Vco2 Mechanical issues Failure to. Reac
Measurement With the peVice Steady State vaporization of water, and the calculation of total body water or
respiratory quotient are factors that might introduce errors in
Air leak >10% High inspired Fio2
around endo Recent interven the estimation of total energy expenditure with this technique.
tracheal tube ( > 6 Q ° % a ) If the necessary conditions are met, the doubly labeled water
lions (suction technique is currently the best method for estimating energy
Air leak ih :the ing, painful expenditure, because expired gas analysis is not required, and
procedure)
circuit serial measurements of stable isotopes in urine samples provide
Calibration issues Fever, seizures, an objective assessment of energy expenditure over a period
Chest tube for dysautonornia
pneumothorax of 4 to 21 days. However, the doubly labeled water technique for
Moisture or obstruc- Recent change in determination of energy expenditure is difficult to use in criti-
tion due to water ventilator set- cally ill children because it requires fluid balance in the steady
in the circuit tings
state. This is a major problem in the critically ill child with
Study period too
short active capillary "leak" syndrome. Hence decreased urinary out-
put, capillary leak syndrome, use of diuretics, or fluid overload
Box 75-1 Suggested Criteria for Targeted Indirect exclude the use of this technique. The isotope costs and avail-
Calorimetry3,51 ability may be concerns, and the doubly labeled water technique
cannot measure brief periods of peak energy expenditure.
Children at high risk for metabolic alterations who are Recently, investigators have proposed hypocaloric diets in
suggested candidates for targeted measurement of REE in the
PICU include the fallowing:
critically ill adults.58,66 Administration of high-calorie (glucose-
 Underweight (BMI <5th percentile for age), at risk of load) diets during the acute phase of illness may exacerbate hyper-
overweight (BMI >85th percentile for age), or overweight glycemia, increase carbon dioxide generation with increased
(BMI >95th percentile for age) load on the respiratory system, promote hyperlipidemia
 Children with >10% weight gain or loss during ICU stay resulting from increased lipogenesis, and result in a
 Failure to consistently meet prescribed caloric goals hyperosmolar state. Hypocaloric diets may have a protein-sparing
 Failure to wean, or need to escalate respiratory support effect, and have demonstrable benefits in critically ill obese patients.
 Need for muscle relaxants for >7 days Overfeeding critically ill children is associated with net
 Neurologic trauma (traumatic, hypoxic, and/or ischemic) with lipogenesis, hepatic steatosis, liver dysfunction, and increased
CO2 production and difficulty in ventilator weaning.55 However,
evidence of dysautonomia
it is uncertain if administration of energy intake lower than the
 Oncologic diagnoses (including children with stem cell or
bone marrow transplant) measured expenditure is appropriate for the critically ill
 Children with thermal injury pediatric patient.
 Children requiring mechanical ventilator support for >7 days In summary, energy expenditure must be carefully evalu-
 Children suspected to be severely hypermetabolic (status ated throughout the course of critical illness using measure-
epilepticus, hyperthermia, systemic inflammatory response ments where available. In patients meeting the requirements
syndrome, dysautonomic storms, etc.) or hypometabolic
for this test, IC provides an accurate measurement of REE.
(hypothermia, hypothyroidism, pentobarbital or midazolam
coma, etc.)
IC may be applied in specific patient groups targeted due
 Any patient with ICU length of stay >4 weeks may benefit to risk of metabolic instability and may help prevent unin-
from IC to assess adequacy of nutrient intake tended underfeeding and overfeeding in these patients. In the
absence of measured REE, equation-estimated REE may be
used. However, the uniform application of stress factors is not
Another method of energy expenditure deter __ nination is advisable and must only be used in individual cases after care-
based on the use of doubly labeled water; however, at this time ful evaluation. Once energy needs are determined, the optimal
the technique remains confined to research settings. Stable substrate required for maintenance of energy needs is mixed
isotope technique has been available for many years and was fuel (glucose and fat). The proportion of each varies accord-
first applied for energy expenditure measurement in humans ing to the clinical situation. See Table 75-2 for recommended
by Schoeller and van Santen78 in 1982. Isotope studies using macronutrient requirements for critically ill children.
doubly labeled water have since been validated and, following
intense and skeptical scrutiny, have now been established as a
"gold" standard for total energy expenditure estimation with
Protein Requirements
widespread application.43,74-77 In this method, stable isotopes of Protein turnover and catabolism are increased several-fold in
water (2H20 and H2180) are administered orally. They mix with critically ill children. An advantage of high protein turnover is
the body water and the 180 is lost from the body as both water that a continuous flow of amino acids is available for the synthe-
and CO2, while the 2H is lost from the body only as water. The sis of new proteins. Specifically, this process involves a redistri-
difference in the rates of loss of the isotopes 180 and 2H from bution of amino acids from skeletal muscle to the liver, wound,
and other tissues involved in the inflammatory response. This
the body reflects the rate of CO2 production, which can be
allows for maximal physiologic adaptability at times of injury
used to calculate the total energy expenditure. This method
or illness. The catabolism of muscle protein to generate glucose
1080 Section V Renal, Endocrine, and Gastrointestinal Systems
—
and inflammatory response proteins is an excellent short-term
adaptation, but it is ultimately limited_because of the reduced
protein reserves available in children and neonates. Although
children with critical illness have increases in both whole-body
protein degradation and whole-body protein synthesis, it is the
former that predominates during the stress response. Children,
especially preterm infants, have reduced macronutrient reserves,
with less than half the protein contenf of adults. "The ill effects
of negative protein balance may not be tolerated by infants and
malnourished children with already decreased or depleted lean
body mass reserves.
- Unlike during starvation, the provision of dietary- carbohy---.
drate alone is ineffective in reducing the protein catabolism or
endogenous glucose production via gluconeogenesis in the
metabolically stressed state.° Therefore, without elimination of
the inciting stress for catabolism (i.e., the critical illness or
injury), the progressive breakdown of muscle mass from critical
organs results in loss of diaphragmatic and intercostal muscle
(leading to respiratory compromise) and the loss of cardiac
muscle.53,54 The amount of protein required to optimally enhance
protein accretion is higher in critically ill than in healthy
children. Infants demonstrate 25% higher protein degradation
after surgery and a 100% increase in urinary nitrogen
excretion with bacterial sepsis.53,54 The provision of dietary
protein sufficient to optimize protein synthesis, facilitate
wound healing and the inflammatory response, and preserve
skeletal muscle protein mass is the most important nutrition
intervention in critically ill children. A supply of adequate
proteins and energy intake improves protein balance by
increasing protein synthesis, although protein breakdown is
not affected. The amount of protein required to maintain a
positive nitrogen balance may vary according to the severity of
illness. Furthermore, the ideal amount and proportion of
amino acids required during critical illness are not known. This
is relevant because amino acids and other nutrients not only
serve a nutritional role but also are actively involved in
physiologic and pathophysiologic processes and may act as
pharmacologic agents. Nitrogen balance varied in critically ill
patients receiving different amounts of branched-chain amino
acids in parenteral formula.55 Sulfur amino acid metabolism in
septic children is impaired, and the rates of cysteine oxidation
are decreased and plasma cysteine fluxes are increased, sug-
gesting increased protein breakdown to supply cysteine and
spared cysteine catabolism by decreased rates of coddation.56
Further studies to determine the individual requirement of
specific amino acids under catabolic conditions are necessary,
particularly in view of the important functions of amino acids,
not only in protein synthesis but as signaling molecules57 and
precursors for important substrates such as glutathione 58 and
methyl group donors.59 Alternatively, excessive protein
administration could be deleterious, particularly in children
with marginal hepatic or renal function. Neonates with higher
protein intakes have been shown to develop azotemia, pyrexia,
and possible long-term detrimental effects on cognitive devel-
opment.6°,61 Hence further studies on specific nutritional and
functional requirements of amino adds are needed.
Lipid Requirements
Nonprotein calories are commonly provided as carbohydrates
(55% to 65%) and fat (35% to 45%). In the absence of ade-
quate lipid supplementation in the diet, critically ill children,
who have depleted lipid stores at baseline, are likely to suffer
essential fatty acid deficiency.67 Lipid administration is gener-
ally restricted to 30% to 40% of the total calories, and after an
initial prescription of 1 g/kg/day, it may be gradually increased
to 2 to 4 g/kg/day, depending on the tolerance level. Triglyc-
eride levels should be regularly monitored for lipid tolerance.
Concentrated lipid formulas (Intralipid 20%) should be used,
given the lirriitation fluid volume for administration of
support.
Micronutrient Requirements
Micronutrients play significant physiologic roles. Beneficial
effects of micronutrients such as tat-soluble vitamins (A, U,
E, and K), water-soluble vitamin (C), zinc, selenium, and folic
acid have been described in selected groups of patients in well-
defined settings. The presumed safety of micronutrients and
probably exaggerated efficacy and generalized applicability to
heterogeneous populations are factors that may be respon-
sible for the widespread prescription of these compounds.62
Commercially available antioxidant nutrients need to be scru-
tinized for optimal dosage and side effects in the clinical set-
ting where they are most likely to be beneficial. Hospitalized
patients, especially those with critical illness, currently receive
these additives in accordance with Food and Nutrition Board
recommendations for daily allowances.
The antioxidant properties of certain micronutrients have
renewed interest in their role during critical illness.63 Vitamins
C and E have important antioxidant activities. Selenium has
also been shown to be a critical micronutrient with antioxidant
functions in patients with thermal injury and trauma." A com-
plex system of special enzymes, their cofactors (selenium, zinc,
iron, and manganese), sulfhydryl group donors (glutathione),
and vitamins (E and C) form a defense system to counter the
oxidant stress seen in the acute phase of injury or illness. Criti-
cally ill patients may have variable deficiencies of micronutri-
ents in the early phase of illness. Vitamins and trace elements
are redistributed from the central circulation to tissues and
organs durinab the systemic inflammatory response syndrome
(SIRS).63 Levels of trace elements, such as iron, selenium, and
zinc, and water-soluble vitamins are decreased, whereas copper
and manganese levels may be increased.65 In addition, trauma
and thermal injuries are characterized by extensive losses of bio-
logic fluids through wound exudates, drains, and hemorrhage,
which cause negative micronutrient balances. The reduced
stores of these enzyme cofactors, vitamins, and trace elements
decrease rapidly after injury and remain at subnormal levels for
weeks. Low endogenous stores of antioxidants are associated
with an increase in free radical generation, augmented systemic
inflammatory response, cell injury, and increased morbidity
and mortality in the critically x.66,67
Recently, there has been increased interest in the role of
vitamin D as an antioxidant. Serum levels of vitamin D are
decreased in children with severe burns." Vitamin D status
may be compromised for months after burn injury. Indeed,
recent studies have reported the prevalence of vitamin D defi-
ciency in the general population.69-73 Future studies examining
the associations between vitamin D deficiency and altered
immunity, infectious risk, arid illness severity are under way.
These studies are expected to highlight the application of
vitamin D replacement in deficient subjects and its role in
influencing outcomes from illnesses. The concept of early
 Chapter 75 Nutrient Metabolism and Nutrition Therapy During Critical Illness
— 1081
micronutrient supplementation to prevent the development
of acute deficiency, to rectify the oxidant-antioxidant balance,
and to reduce oxidative-mediated injuries to organs has driven
recent trials in critically ill patients.74 Antioxidant research in
the critically ill has focused on copper, selenium, zinc, vita-
mins C and E, and the vitamin B group. Most of these studies
were performed in relatively small patient populations pre-
senting with heterogeneous diseases, such as trauma, burns,
sepsis, or acute respiratory distress syndrome, however, and
thus are underpowered to detect a treatment effect on clini-
cally important outcomes. Heyland and colleagues
performed a systematic review of trials supplementing critically
ill patients with antioxidants, trace elements, and vitamins with an
aim to improve sunrival.63 They concluded that trace elements
and vitamins that support antioxidant function, particularly
high-dose parenteral selenium alone or in combination with
other antioxidants, are reportedly safe and may be associated with
a reduction in mortality in critically ill patients.
Electrolyte management in critically ill children can be com-
plicated because of existing deficiencies, fluid shifts, increased
insensible losses, drainage of bodily secretions, and renal fail-
ure. Intravenous fluids or parenteral nutrition (PN) prescrip-
tions need to be reviewed daily in light of the basic electrolyte
and blood sugar levels. In children with significant gastroin-
testinal fluid loss (gastric, pancreatic, small intestinal, or bile),
the actual measurement of electrolytes from the drained fluid
may assist in prescribing replacement fluids. Acute changes
in serum electrolytes that require urgent electrolyte replace-
ment must not be managed by changes in the PN infusion
rate or composition, because this method may be imprecise
and potentially dangerous. Phosphate and magnesium levels
are often abnormal in critically ill children, especially in those
with existing nutritional deficiencies, sepsis, or ongoing nutri-
tional deprivation.
Enteral iutrition i Critically
Children
Enteral nutrition (EN) is the preferred mode of nutrient
intake in critically ill patients with a functional gastrointesti-
nal system, due to its lower cost and complication rate when
compared to parenteral nutrition (PN).51 Early institution of
EN is associated with beneficial outcomes in animal models
and human studies63 and has been increasingly implemented
during critical illness, often using nutrition guidelines or
protocols.75 Early enteral nutrition has been shown to decrease
infectious episodes and decrease the length of hospital stay in
critically ill patients.76 Pediatric studies have shown successful
implementation of early enteral nutrition using institutional
protocols.75,77 Figure 75-2 provides an example of an approach
to instituting and maintaining EN in the PICU. Although
early EN has been adopted in most units, subsequent mainte-
nance of enteral nutrient delivery remains elusive, as EN is fre-
quently interrupted in the intensive care setting for a variety of
reasons, some of which are avoidable.30,78 Frequent interruptions
in enteral nutrient delivery may affect clinical outcomes
secondary to suboptimal provision of calories and reliance
on PN. It has been reported that EN is interrupted in a third
of patients in the PICU who were started on EN.29 EN was
frequently interrupted for avoidable reasons. Patients experi-
encing avoidable EN interruptions had more than a threefold
increase in the use of PN and significant delay in reaching
caloric goals. This collaborative study, examining bedside
nutrition practice, illustrates some of the challenges to the
provision of nutrition support and highlights opportunities
for practice modification. Fasting for procedures and intoler-
ance to EN were the commonest reasons for prolonged EN
interruptions. Interventions aimed at optimizing EN delivery
must be designed after examining existing barriers to EN and
directed at high-risk individuals who are most likely to benefit
from these interventions. Knowledge of existing barriers to
EN, such as those identified in this study, will allow appropri-
ate interventions to be planned. Intolerance to enteral feeds
may be a limiting factor, and supplementation with paren-
teral nutrition (PN) in this group of patients allows earlier
optimal nutritional intake. Taylor and colleagues reviewed
nutritional delivery in a group of 95 children in a PICU over
a 12-month period and made similar observations. 79 Chil-
dren received a median of 58.8% (range 0% to 277%) of their
estimated energy requirements in this investigation. Enteral
feeding was interrupted on 264 occasions to allow clinical pro-
cedures. Rogers and colleagues reviewed nutritional intake in
42 patients admitted to an Australian tertiary-level PICU over
458 ICU days.3° When actual energy intake was compared
with estimated energy requirement, only 50% of patients
had received their full estimated energy requirements after a
median of 7 days in the ICU. Prolonged fluid resuscitation
is a major factor hindering the achievement of estimated energy
requirements, despite maximizing the energy content of feeds.
Other contributing factors included interruption of feeds for
procedures, enteral feed intolerance, and cooling. Protocols
for use of transpyloric feeding tubes and changing from bolus
to continuous feeds during brief periods of intolerance are
strategies to achieve estimated energy requirements in this
population. Box 75-2 summarizes some of the barriers to suc-
cessful enteral feeding in the PICU.
The role of enteral nutrition has expanded beyond that of
growth and nutritional rehabilitation. Newer components
introduced in enteral feeds include 1-arginine, glutamine,
taurine, nucleotides, omega-3 and omega-6 fatty acids, carni-
tine, growth factors, probiotics, and probiotics. Disease- and
health-modulating effects of these additives are becoming
increasingly understood, and they may have application in the
management of a subset of critically ill children with specific
illnesses.
Enterally administered feeds meet nutritional requirements
in critically ill children with a functional gastrointestinal sys-
tem and have the advantages of cost, manageability, safety, and
preservation of gastrointestinal function. Early introduction
of enteral feeds in critically ill patients helps to achieve posi-
tive protein and energy balance and restores nitrogen balance
during the acute hypermetabolic state of illness. Enteral nutri-
tion elicits release of growth factors and hormones that main-
tain gut integrity and function.8 Despite its perceived benefits,
current practice in ICUs indicates a significant proportion of
eligible patients are deprived of enteral feeds.36 An aggressive
protocol for early intragastric feeding was applied to 71 critically
ill children, using full-strength enteral formula started within
12 hours of enrollment and advanced to target volumes of energy
intake.1° In this study, increases in caloric intake were well-tol-
erated by the children and reached predicted basal metabolic
rate by day 1 and predicted REE by day 4. Children who were
successfully fed had a lower mortality than those who did not
respond to the early poststress intragastric feeding. The majority
1082 Section V — Renal, Endocrine, and Gastrointestinal Systems
 Oral route unavailable CONSTIPATION
________ OR
(For age >1 morithinon'-neutropenic
Unable to Protect airway
NO STOOL AFTER 48 HOURS OF EN
'essrn
weight :ass on ion
identify•Niltri ...iscalondg9d •" Day #1:
 Prune
HEAD OF BED elevated 30°
juice
unless contraindicated7
Day #2
EVALUATE.FOI4*.RISKCiFASPIji010.N7.::'
Glycerin sup
..(DepresSedgagldough; altered tehaoritirh,:. .

:Docueate
elaYed.gaStriO:eMPtY.ing GE reflux,•, •
. "(3:Yr"S;-p0-;10 mg BI
.-

severe • bronchospasm, history of ,reflUx) yrs: P0.20 :mg BID):

(5712 Yea: P0 50.'mg-BID):, _
yrs: P0100 mg
(–) NO •
(+) ASPIRATION
RISK ASPIRATION RISK
Senna (Discontinue after 2 norma
stools)
ThANSPYY-QRIC NASOGASTRIC/gastric 2 . 5 mL:
.
Naspiejunal/gastrojejdnal tube FEEDINGS BS.:. yrs: P0 3.75 mL BID)
•E .

 : Bs present/no.gastric.:. mL BID)
FEEDINGS
distension (>12 yrs: Pai Tab BID): •
With gastric decompression:
(–) ABNORMAL (+) NORMAL Fleet enema (for age >2 yrs): ,
GASTRIC GASTRIC Pediatric Fleets enema: 2-12 yrs
 Figure 75-2. Enteral nutritional support algorithm. (Modified from Mehta NM.- Approach to enteral feeding in the PICU, Nutr Clin Pratt 24277, 2009.)

of children who did not respond to the early enteral feeding

strategy were sicker and exhibited nonreversible septic shock
and significantly lower ejection fractions on echocardiography.
Enteral feedings are indicated early in the course of critical
— illif peristalsis h.-as-been establithed. Postpyloric feedings
are recommended because of gastric distension and hypo-
motility. Feeds can be administered into the stomach or jeju-
num With the aid of feeding tubes inserted nasally or orally.
intragastrk or intrajejunal feeding tube tip placement should
be confirmed by radiography. Softer tubes constructed from
silicone or polyurethane may be inserted using stylets at the
bedside. Insertion ofjejunal feeding tubes may require fluoro-
scopic or en-doscopic guidance.
Postpyloric tubes provide the opportunity to feed a subset
of children for whom intragastric feeding has not succeeded
or is deemed unsafe. Postpyloric feeding is increasingly
 Chapter 75 — Nutrient Metabolism and Nutrition Therapy During Critical Illness 1083
Box 75 2 Barriers to EN Delivery n the PICU
-
Fasting before procedures
 Enclotracheal tube—related procedures (incubation,
extubation)
 Major operative procedures
 Other procedures requiring general anesthesia
 Bedside procedures requiring sedation
 Radiology suite or interventional radiology procedures
Fluid restriction
Delay in establishing enteric tube for feeding
 Delay or difficulty in enteric tube placement
 Malpositioned, obstructed, or displaced enteric tube
Gastrointestinal dysfunction
 Malabsorption, diarrhea, or severe constipation
 Ileus associated with opioid use or postoperative status
Patients at risk of aspiration of gastric contents Holding EN
for perceived intolerance
 High gastric residual volume
 Abdominal distension or discomfort
 Vomiting or diarrhea
Failure to implement evidence-based uniform algorithmic
approach to EN
 Delay in initiating EN
adopted to feed children with reflux or delayed gastric emp-
tying who are at risk for aspiration. Placement is not always
successful, and a variety of novel techniques have been used to
facilitate postpyloric placement. These methods rely on grav-
ity and gut peristalsis to advance the tube tip past the pylo-
rus. Because difficulty in tube placement can be anticipated in
some patients, endoscopy or fluoroscopy guidance should be
used, which avoids the rare occurrence of adverse events (such
as perforation) and pancreatitis seen during blind enteral tube
placement.
Surgical placement of gastrostomy or jejunostomy tubes
allows long-term enteral feeding and administration of drugs
in selected patients during intensive care and after discharge
from the ICU. The advent of percutaneously placed gastric
and jejunal tubes has minimized cost, time, and morbidity.
Stoma site infection, obstruction, and tube dislodgment are
common complications and must be identified and managed
early. Tube tip malposition is frequently encountered with
any of these devices either at placement or during the course
of their use. Bedside screening methods for ascertainment of
correct tip position range from auscultation during air insuf-
flation to ultrasound-guided tip localization. However, feeds
should be held when malposition of tip is suspected; when
in doubt, radiographic confirmation of correct tip position
should be obtained before recommencing feeds.
Immune-Enhancing Diets for the Critically
III Child
In 1996, Bone and colleagues80 outlined the role of the com-
pensatory antiinflammatory response (CARS), which follows
the initial proinflammatory response by the body challenged
with an insult or infection. The antiinflammatory response
was believed to be the second phase of a biphasic, highly coor-
dinated inflammatory response and was aimed at keeping
the proinflammatory response under control. It is clear that
immunomodulation plays a significant role in the nature of
response to infectious insult and impacts outcome in children
with sepsis admitted to the ICU. Therapies aimed at modulat-
ing or stimulating the immune response have yet to be vali-
dated in children.
Immune-enhancing diets (IEDs) have been available for
many years, and their role in the care of critically ill patients
remains controversial. An increasing number of studies exam-
ining the effect of IEDs in various clinical populations and
related meta-analyses continue to provide conflicting conclu-
sions. Methodological flaws in conducting initial studies and
the heterogeneous nature of the IED formulations used do not
allow for dispelling current doubts regarding the safety and
efficacy of these diets. The commercially available diets con-
tain a mixture of compounds in varying doses, and the role of
individual compounds is impossible to interpret. The immu-
nomodulating effects of individual compounds are dose-
dependent, and mixtures of different immunomodulating
nutrients may have synergistic but also antagonistic effects.
However, the compositions of the products compared in the
meta-analyses are considerably different.
In a meta-analysis of randomized clinical trials examin-
ing the efficacy of enteral immunonutrients in adult patients,
Heyland and colleagues selected 22 human studies, which
included 2419 subjects. 8' There was no difference in mortal-
ity between the two groups, although patients who received
enteral immunonutrition had a decreased incidence of noso-
comial infections and decreased length of hospital stay com-
pared with patients who received a standard enteral formula.
The authors analyzed a subgroup of 13 trials involving criti-
cally ill patients. Duration of hospital stay was decreased in
the experimental arm in this subgroup (treatment effect 0.47 –
days; 95% confidence interval [CI] –0.93 to –1.01 days).
When this subgroup of investigations was further subdivided
into trials using experimental formulas with high arginine ver-
sus those using lower arginine content, mortality was noted to
be higher in the studies using relatively lower arginine content
formulas (risk ratio, 2.13; 95% CI, 1.08 to 4.21). A statistically
insignificant trend toward decreased infectious complications
in the high arginine group was reported. The high arginine
group was associated with a shorter duration of hospitaliza-
tion. This overview did not address the issue of the cost of
intervention. Although an overall effect on mortality was not
seen with immunonutrition intervention, some studies in the
overview showed contrasting results. The study by Bower et
al.82 (n = 296) comparing IMPACT with Osmolite HN for-
mula in critically ill adults demonstrated increased mortality
(15.7%) in the immunonutrition (IMPACT) group versus the
control group (8.4%). A subgroup analysis of patients desig-
nated as septic at baseline showed that mortality in the experi-
mental arm (IMPACT) was almost three times higher (11/45
[25%]) than that in the control arm (4/45 [8.9%] ).
A multicenter trial comparing enteral immunonutrition
with PN conducted an interim subgroup analysis based on
some reports suggestive of increased mortality in critically ill
patients receiving immunonutrition.83 Interestingly, the study
was discontinued after the interim analysis. Analysis of 39
patients with sepsis or septic shock included in this interim
analysis indicated mortality in the immunonutrition enteral
arm (8/18 [44.4%]) was three times higher than that in the PN
arm (3/21 [14.3%]).
Decreased length of hospital stay and decreased nosocomial
infections in the treatment group were beneficial secondary
1084 Section V Renal, Endocrine, and Gastrointestinal Systems
e 75 5 Individual Imrnunonutrients and Potential Effects
Adult Populatio
Nutrient General Septic
Arginine No benefit
.
Glutamine , . PN.benefici.albeneficial
CireCeiitirig EN).
Ornega-3 FFA
Antioxidarrks . Possible benefit`
FFA; Free fatty acids.
Modified-from-Lee S. Gura KM, Kim S,-et al: Current clinical applications_of omega,6 nd omega-3 fatty acids,.Nuts Clin Pract 21(4323-341, 2006.
outcomes reported by each of the three reviews/meta-anal-
yses of studies examining the use of IEDs. In summary, no
conclusive data on the beneficial effects of IEDs have been
established. Proponents of immunonutrition argue that the
inability to achieve goal volume of enteral feeds in most of the
studies may be responsible for the lack of favorable effect on
outcomes. ICU patients are heterogeneous, and the timing of
intervention may be important in this subgroup of patients.
The severity of illness in some patients may not be amenable
to manipulation by immunonutrients, and careful selection
of patients is essential to demonstrate benefit in subgroups.
Future research should investigate the role of individual nutri-
ents in select groups of patients. The novel concept of phar-
maconutrition has been proposed where a disease-dedicated
nutrition therapy is developed following a rigorous step-by-
step procedure.84 Nutrients are selected according to their
pharmacological properties and after an in-depth evaluation
of their biological interactions when mixed together. Table
75-5 summarizes a list of nutrients and their beneficial effects
in specific populations in critical illness. The optimum admin-
istration schedule (i.e., dose, route, timing and duration) of
the new formulae is then determined in well-conducted pro-
jective clinical trials where it is administered apart from the
standard nutrition to ensure full delivery of the expected doses.
Dose-response effect then identifies the essential components
of immunonutrition at the correct doses. Future studies are
required to prove if a critical volume must be reached in order
to demonstrate a beneficial effect of these immunonutrients.
There are insufficient pediatric studies evaluating the role of
nutrition-based immunonutrition in critically ill children.
The generalized use of immunonutrition for children in the
PICU cannot be recommended.
P a r e r t e r al ut r i t i on
PN, or hyperalimentation, bypasses the gut, and instead
utilizes intravenous administration of macronutrients and
macronutrients to meet the nutritional requirements of
the body, either partly (as a supplement to enteral feeds) or
entirely (total PN). PN is indicated in children who are unable
to tolerate enteral feeds for prolonged periods. In the setting
of intact intestinal function, PN is not indicated if enteral
feeds alone can maintain nutrition. Although widespread in
its application, PN is associated with mechanical, infectious,
-
intl-rrietabtilit -complications and hence should-be-used only in
carefully selected patients.
Fluid and electrolyte status guides the initial PN pre-
scription. Fluid restrictions limit the amount of calories
is Critica
Trauma Burns :.Acute Lung Injury:
eneficial
Box 75-3 Calculatmg Parehteral Nutrition Calories. -
Total carbohydrate (g): CHO/day x 3.4 kcal/g = CHO calories
1 g dextrose provides 3.4 kcal (most other CHO provide 4
kcal/g)
10% dextrose = 10 g dextrose/100 mL
Total protein (g): Protein/day x 4 kcal/g = Protein calories
1g protein provides 4 kcal
Total fat (20% lipids) (mL) x 2.0 kcal/mL = Lipid calories
(10% lipids = 1.1 kcal/mL)
Total calories = CHO + Protein Lipid calories
Total nonprotein calories = CHO + Lipid calories
delivered, despite use of a concentrated formula. PN should
not be used for replacing ongoing losses. PN should be pre-
scribed daily and after reviewing levels of electrolytes and
blood sugar in order to allow adjustments in the macronu-
trient and micronutrient composition. The patient's hydra-
tion, size, age, and underlying disease dictate the amount of
the fluid to be administered. Box 75-3 describes the calcula-
tions use to determine calories obtained from macronutri-
ents in PN.
Carbohydrates
Carbohydrates are the major nonprotein source of energy.
D-glucose is provided in the monohydrate- form for intrave-
nous administration and yields 3.4 kcal/g. The concentration
of the dextrose solution should not exceed 10% for peripheral
administration. In the setting of central venous access, a range
of concentrations (5% to 40%) can be prepared. Higher glucose
concentration makes the solutions hyperosmolar and may cause
phlebitis or thrombosis and decrease the lifespan of the vessel
when PN is administered peripherally through a vein. Blood
glucose estimations must be followed carefully given the
increased incidence of hyperglycemia, especially in young
infants. Carbohydrate is started at 5 to 8 mg/kg/min. Gradually
increasing the carbohydrate load allows an appropriate
endogenous insulin response and prevents fluctuations in blood
sugar. Abrupt cessation of PN may result in hypoglycemia and
should be anticipated and avoided. 85 Fat is supplied as intralipid;
which provides the othersource-of-calories---- in PN and reduces
carbon dioxide production and the water retention that is seen
when carbohydrate is the sole source of calories.
 Chapter 75 — Nutrient Metabolism and Nutrition Therapy During Critical Illness 1085

PRECURSOR OF EICOSANOIDS
Arachidonic Eicosapentaenoic
acid acid
120:4n6 I 120:5n3 .I
Cyclo- Lipoxy- Cyclo- Upoxy-
oxygenase genase oxygenase vgenase

Protanalds . Leukotrienes .PrOtanoids eukotri ones

PGE2; LT134 PGE3 LTB5
PGI2 13C4 PGI3 LTC5
TXA2 LIE4 .TXA3 13E5

Pro-inflammatory Anti-inflammatory
Amino Acids
PGE2:.prostaglandin E2 .PGE3:prostaglandin.E3
PGI2 prostacyclin PG13::prostaglandin 13:
TXA2: thrOrriboxand A2 TXA2: thromboxane
I.TB4:teukOtriene B4 LTB5leukotneneB5
ieuKotriene C4 LTC5;lebkotriene'C5..
LTE4: leukotriene E4 LTE5 leukotriene',E5
One gram of protein yields 4 kcal. The initial recommended
dosage range from 0.5 to 3 g/kg/day is based on age, disease
state, and individual requirements. The usual available con-
centrations are between 1% and 4%, although patients with
hepatic disease, renal insufficiency, and children with meta-
bolic diseases (e.g., maple syrup urine disease) should receive
appropriately modified concentrations. TrophAmine contains
a higher percentage of branched-chain amino acids and a small
amount of glycyl-cysteine. This solution is mainly used in the
neonatal population. It is recommended and used in patients
with hepatic encephalopathy and in children on long-term PN
(e.g., short bowel), although data supporting this application
are scarce. There is an increasing interest in the use of gluta-
mine in PN. Glutamine, along with cysteine as glycyl-cysteine,
is a precursor for glutathione, which is a major antioxidant.
Glutamine is also a precursor for nucleotide synthesis, and
although it is a nonessential amino acid, it can become condi-
tionally essential, especially in catabolic states such as sepsis and
trauma. Glutamine has a short shelf life. However, its applica-
bility has been widespread. It has been introduced in PN solu-
tions for its presumed benefits, such as restoration of protein
and nitrogen balance, attenuation of gastrointestinal mucosal
atrophy, and reduction of bacterial translocation and bactere-
mia after chemotherapy. The National Institute of Child Health
and Development (NICHD) neonatal research network did
not find significant differences in outcomes when a multicenter
study randomized 1430 extremely low-birth-weight neonates
to PN containing 20% glutamine or an isonitrogenous control.
However, pediatric burn patients have been shown to have
deficient peripheral glutamine production. In a double-blinded
randomized control trial, glutamine-enhanced PN reduced
gram-negative bacteremia in severely burned patients."
Lipids
Lipids represent an integral part of PN and provide energy
derived through fatty acid oxidation. Lipids are usually started
at 0.5 to 1 g/kg and advanced to a maximum intake of 3 g/kg
clinical applications of omega-6 and omega-3 fatty adds,
Nutr Clin Pract 21141:323-341, 2006.)
or a maximum 60% of total kilocalories. Lipid calories allow
for a lower concentration of carbohydrate (lower osmolarity
of PN). Lipid emulsions are available as 10% (1.1 kcal/mL) or
20% (2 kcalimL). Intralipid prevents or treats essential fatty
acid deficiency. The total lipid usually is delivered over an 18-
to 24-hour period through separate tubing, using a Y-connec-
tor near the infusion site. Delivery of amino acid, glucose, and
lipid (three-in-one) is no longer recommended for neonatal
patients because of the risk of calcium phosphate precipitation
being obscured by lipid in the preparation.
Lipids are a crucial source of nutrition in parenteral for-
mulas. Traditionally considered a calorie-dense nutrient and
a source of essential fatty acids, lipids in intravenous feeding
regimens have added advantages, such as providing a more
balanced energy expenditure and facilitating better respira-
tory function parameters. Fatty acid derivatives are major bio-
logic modulators.87 Figure 75-3 illustrates the basic pathways
and inflammatory effects of fatty acid metabolites. The lin-
oleic acid load, as a consequence of predominantly soy-based
lipid in current formulations, results in increased arachidonic
acid production and decreased production of eicosapentae-
noic acid (EPA) and docosahexanoic acid (DHA).88 Increased
arachidonic acid levels may increase the proinflammatory
cytokine production and activity. EPA levels may influence
the production of antiinflammatory cytokines, 87 and DHA
has been shown to lower blood pressure, improve endothelial
function, and elevate levels of high-density and low-density
lipoproteins.89 Thus DHA and EPA, found in fish and fish oils,
are essential fatty acids for humans. In an attempt to decrease
the linoleic acid intake, soy-based oil has been partly replaced
by medium-chain triglycerides, olive oil, or fish oil in intra-
venous emulsions. The metabolic roles of omega-3 polyun-
saturated fatty acids are emerging. Parenteral fish oils may
have immune modulatory function and have been applied
for their beneficial effect in the perioperative period follow-
ing major abdominal surgely.34'86 Further research examining
the efficacy and safety of different triglycerides, derived from
medium-chain triglycerides, olive oil, and fish oils, will allow
their application in specific disease conditions. Furthermore,
in this era of nutrigenomics, the effect of fatty acids on genes

Figure 75-3. Omega-3 and omega-6 Fatty add metabo-

lites. (Adapted from Lee S., Gura KM, Kim .5, eta!: Current
1086 Se ion V --- Renal, Endocrine, and Gastrointestinal Systems
and proteins is being increasingly elucidated and will influ-
ence clinical practice_: In the future, designer lipid formula-
tions and molecules may be applied in parenteral or enteral
nutrition regimens for their beneficial effects in specific dis-
ease conditions.
Electrolytes/Minerals and Trace
Elements
All solutions are typically prepared with minimum acetate
(i.e., all salts are added as chloride) unless prescribed other-
wise. It is possible to prescribe an all _acetate.._ solution with
no chloride. Calcium and phosphorus precipitate when their
concentrations exceed an allowable-limit-related-to-the-solu-
bility index of (Ca)3(PO4)2 and the pH of the solution. Sele-
nium may not be routinely added to PN. A serum selenium
level should be obtained if a patient requires PN for more
than 30 days without enteral intake. Multivitamins and trace
elements are routinely added to the PN, and recommended
intakes are elucidated dsewhere.9° Heparin usage in PN is
practiced in many centers and has been shown to decrease
catheter-related sepsis.91 Heparin in concentrations of 0.5 to
1 U/mL is thought to prevent thrombosis and possibly phle-
bitis in peripheral lines, although there are no controlled trials
showing significant benefit of heparin usage in PN.
Biochemical Monitoring
A PN profile is recommended at initiation of therapy and
weekly thereafter. The profile includes serum levels of sodium,
potassium, chloride, glucose, carbon dioxide, blood urine
nitrogen, creatinine, albumin, magnesium, phosphate, total
and direct bilirubin, and transaminases. For children requir-
ing PN for more than 30 days, selenium, iron, zinc, copper,
and carnitine levels should be checked. Daily vital statistics
and routine anthropometry must be monitored to ensure
adequate growth and development. Critical care units ben-
efit from the expertise of a dedicated nutritionist, who should
be consulted on a regular basis to guide optimal nutritional
intake of patients.
Central venous access is required for delivery ofhyperosmo-
lar PN solutions into a large-bore vein with high-volume blood
flow, to prevent thrombosis and phlebitis (see Chapter 15).
The incidences of infective and.life-threatening complications
related to indwelling central lines have necessitated extreme
caution with central PN use.92,93 Central lines should be placed
by experienced operators and line tip position confirmed
by radiography before the lines are used for PN delivery. It
is recommended that central line tips be positioned outside
the cardiac chambers at all times. Central lines are recom-
mended for delivery of infasates with osmolarity greater than
900 mOsm/L (10% dextrose, 2% amino acids with standard
additives).
Refeeding Syndrome
Aggressive nutritional rehabilitation in malnourished patients
or after prolonged starvation results in a constellation of bio-
chemical and-clinical:features-with cardiopulmonary compli-
cations: This well-described entity is called refeeding syndrome
and is often unrecognized. Hypophosphatemia is the hall-
mark of refeeding syndrome, which is also associated with
hypomagnesemia, hypokalemia, and fluid retention. Patients
admitted to the PICU with nutritional deficiencies, those with
Chronic conditions causing malnutrition or those fasted for ro-
to 14 days are at risk of refeeding syndrome following aggres-
sive oral, enteral, or parenteral nourishment. Introduction of
nutrition in these patients stimulates anabolism, with a switch
from protein and fat catabolism to predominantly carbohy-
drate metabolism. Glucose becomes the primary energy source, ---
leading to insulin release. Insulin-mediated cellular uptake of
glucose causes intracelular shift of phosphate, potassium, and
magnesium, thus rapidly lowering their serum levels. Insulin
also causes sodium and fluid retention with rapid expansion
of extracellular fluid volume. The clinical manifestations of
refeeding syndrome are a result of the dyselec-trolytemia and
fluid overload, and involve cardiorespiratory, neuromuscular,
and hematologic complications. Hypotension, respiratory fail-
ure, muscular weakness, confusion, seizures, coma ,and even
death may result from refeeding syndrome.
Awareness of this syndrome, identification of at-risk patients
and gradual introduction of nutrition in these individuals help
prevent the refeeding syndrome. Calories may be introduced
at 25% to 50% of requirement and increased 10% to 25% daily
until the caloric goal is met. Careful monitoring of electro-
lytes and vigilance for clinical manifestations of the syndrome
allow early detection of complications, and feeds are advanced
in the setting of biochemical stability. Prompt correction of
electrolyte abnormalities, close attention to fluid balance, and
supplementation with multivitamins will help avoid the car-
diorespiratory sequelae from refeeding in the critically ill child.
Nutritional Support of Obese
Critically ill Children
Overweight/obesity continues to increase in children and
adolescents, and annual obesity-related hospital costs in 6- to
17-year-olds have reached $127 million per year. The severity
of obesity is classified based on BMI into the following three
categories: (1) overweight = BMI 25 to 30 kg/m2, (2) obesity =
EMI 30 to 40 kg/m2, and (3) morbid obesity = BMI greater
than 40 kg/m2. Overweight children and adolescents are
increasingly being diagnosed with impaired glucose tolerance
and type II diabetes, and they show early signs of the insulin
resistance syndrome and cardiovascular risk. Centralized dis-
tribution of body fat is associated with the risk of metabolic
syndrome. Metabolic syndrome is observed in obese children
and is characterized by visceral obesity, insulin resistance,
and dyslipidemia. There is a high risk for type 2 diabetes and
cardiovascular complications in patients with metabolic syn-
drome. Grossly overweight patients are prone to sleep apnea
syndrome, restrictive lung disease, venous thrombosis, mus-
culoskeletal degenerative disorders, hepatic steatosis, and
metabolic disorders associated with bariatxic surgery.
The metabolic response to stress in obese critically ill
patients is complex, given that it occurs in a population with
preexisting major metabolic and endocrine alterations. In
critically ill obese patients, the pattern of substrate oxidation
is mainly protein and glucose, with decreased fat oxidation.94
The extent of protein breakdown is greater than in nonobese
critically ill adults No data on metabolic abnormalities of
obese children are available. In the adult critically ill popula-
tion, hypocaloric nutrition estimated for ideal weight has been
recommended.° The limited adult literature suggests that
 Chapter 75 — Nutrient Metabolism and Nutrition Therapy During Critical Illness 1087

Box 75-4 Guidelines or Pediatric Critical Care Nutritional Support

Number Guideline Recommendations Grade

1A Children admitted with critical illnesses should undergo nutrition screening to identify those with existing
malnutrition and those who are nutritionally at risk.
1B A formal nutrition assessment with the development of a nutrition care plan should be required, especially in
children with premorbid malnutrition.
2A Energy expenditure should be assessed throughout the course of illness to determine the energy needs of criti-
cally ill children. Estimates of energy expenditure using available standard equations are often unreliable.
2B In a subgroup of patients with suspected metabolic alterations or malnutrition, accurate measurement of
energy expenditure using indirect calorimetry (IC) is desirable. If IC is not feasible or available, initial energy
provision may be based on published formulas or nomograms. Attention to imbalance between energy intake
and expenditure will help prevent overfeeding and underfeeding in this population.
3 There are insufficient data to make evidence-based recommendations for macronutrient intake in critically ill E
children. After determination of energy needs for the critically ill child, the rational partitioning of the major
substrates should be based on understanding of protein metabolism and carbohydrate and lipid-handling during
critical illness.
4A In critically ill children with a functioning gastrointestinal tract, EN should be the preferred mode of nutrition C
provision, if tolerated.
4B A variety of barriers to EN exist in the PICU. Clinicians must identify and prevent avoidable interruptions to EN D
in critically ill children.
4C There are insufficient data to recommend the appropriate site (gastric vs. postpyloric/transpyloric) for enteral
feeding in critically ill children. Postpyloric or transpyloric feeding may improve caloric intake compared with
gastric feeds. Postpyloric feeding may be considered in children at high risk of aspiration or those who have
not responded to a trial of gastric feeding.
5 Based on the available pediatric data, the routine use of immunonutrition or immune-enhancing diets/nutri- D
ents in critically ill children is not recommended.
6 A specialized nutrition support team in the PICU and aggressive feeding protocols may enhance the over-
all delivery of nutrition, with shorter time to goal nutrition, increased delivery of EN, and decreased use of
parenteral nutrition. The effect of these strategies on patient outcomes has not been demonstrated.
From Mehta NM, Compher C: A.S.P.E.N. clinical guidelines: nutrition support of the critically ill child, J Parenter Enteral Nutr 33(3)260-276, 2009.

protein requirements are higher in critically ill adult obese
patients. It is recommended that fat be administrated spar-
ingly, mainly to prevent essential fatty acid deficiency.95 No
data on the best nutritional support of critically ill obese chil-
dren are available. Routine equations for tend to overestimate
energy expenditure in obese patients. Energy requirement
in this group should be guided by IC measurement of REE,
where available. When REE is estimated, there is no consensus
on the use of ideal body weight versus adjusted body weight.
As the incidence of obesity in children admitted to the PICU
is rising, future research aimed at addressing some of these
knowledge gaps is desirable.
Guidelines for Pediatric Critical
Care Nutrition
Due to the complexities of critical care, nutrient intake dur-
ing critical illness is challenging (Box 75-4). The lack of robust
evidence for many of the bedside decision-making around
nutrition support in the PICU has resulted in heterogeneity
in practice. Optimal nutrition support in the PICU cannot be
achieved unless there is some uniformity in practice based on
evidence or consensus and an attempt to systematically evalu-
ate practice parameters for feasibility, efficacy, and impact on
patient outcomes. However, the direct effect of nutritional
strategies in a heterogeneous cohort of patients with varying
degrees of illness severity is difficult to assess. Multiple factors
influence outcome during critical illness. Due to these chal-
lenges, current literature is scarce and guidelines for pediatric
critical care nutrition have been based on few good studies but
mainly on smaller studies of expert opinion. In 2009, the Amer-
ican Society of Parenteral and Enteral Nutrition published the
revised guidelines for pediatric critical care nutrition practice.51
These guidelines were based on the best available evidence and
help clarify the principles guiding nutrition therapy in the
PICU population. Early enteral nutrition is recommended in
critically ill children with a functional gastrointestinal tract.
Careful assessment or measurement of energy expenditure
with attention to unintended energy imbalance (due to under-
feeding or overfeeding) seems prudent. Health care workers
must work in a collaborative fashion to identify and prevent
common barriers to nutrition support in the PICU. The appli-
cation of indirect calorimetry and postpyloric feeding is cur-
rently limited to centers with available expertise and resources.
Conclusions
The accurate assessment of nutritional needs and the provision of
individually tailored optimal nutrition support to the critically ill
child are important goals of pediatric critical care. Malnutrition
 1088 Section V Renal, Endocrine, and Gastrointestinal Systems
—

and obesity are prevalent in the critical care population and have
a significant influence on the outcome of critical illness. Further-
more, the hypermetabolic stress response places demands on the
critically ill child that must be met with evidence-based nutrient
supplementation. Intensivists must remain alert to the possibility
of both underfeeding and overfeeding in order to prevent
unintended cumulative energy imbalances in critically ill children.
A multidisciplinary effort to overcome common barriers to
nutrient delivery and the use of evidence-based algorithms will
help achieve nutrition goals in the PICU.
Interest in immune-modulating effects of nutrients, micro-
nutrient supplementation, and the role of newer sources of
lipid formulations has introduced the concept of pharmaco -
sibility ofthis strategy in th-e-PICU will need-t-o-be examined in the
setting of carefully designed studies. In the future, patients will
benefit from individually tailored nutritional regimens suited to
the type and stage of their illness. There are a number of
knowledge gaps that need to be addressed by collaborative
research. Until then,-a multidisciplinary—effort must be made-to
increase awareness of nutritional issues, adherence to institutional
guidelines, and prioritization of nutrition support the PICU.
References are available online at http://www.expertconsult.
corn._____________________________________________

n-utrientsTbut-its-b ene fits-on-ou tcom e-in-the-P GU-have-n o t

been realized yet. Strict glycemic control is associated with a
significant increase in the incidence of hypoglycemia. The fea-