Introduction

Providing adequate nutrition to support growth and development during infancy and childhood is critically important to a child’s overall well being. Malnutrition, occurring when the body does not receive appropriate and/or sufficient nutrients to support proper function, increases the risk of chronic infection, poor wound healing, surgical complications and potentially death. Although this is generally thought to be a more prevalent issue in developing countries, malnutrition in the United States occurs most commonly in acute and chronically ill children.

Although nutritional complications are often associated with receiving too few calories, obese children are also at increased risk for morbidity and mortality from poor nutrition. Obesity in childhood is defined as a weight for length greater than the 95th percentile or a body mass index (BMI) at or above the 95th percentile using growth charts from the Centers for Disease Control and Prevention [1]. Globally, obesity in childhood is defined as a BMI greater than three standard deviations from the World Health Organization BMI medians [2]. Morbid obesity is defined in adults as a BMI of greater than or equal to 40 or a BMI greater than or equal to 35 together with an obesity related health complication.

Healthcare professionals must be vigilant in screening for malnutrition in children and providing realistic goals for its correction. However, accurately assessing a child’s overall nutritional status in a timely fashion and determining optimal needs continues to be difficult and is largely based on best available estimations.

Content in this topic is referenced in SCORE Nutrition overview

Epidemiology

Malnutrition is frequently categorized as either acute or chronic. Acute malnutrition is based on a child’s weight compared to the mean for age whereas chronic malnutrition is based upon height or length for age.

Weight

1 to 2 SD below mean

2 to 3 SD below mean

greater than 3 SD below mean

malnourished

moderately malnourished

severely malnourished

SD - standard deviation

Overnutrition is also a form of malnutrition and in fact is becoming as common as undernutrition in North America. Indeed, nearly 20% of children in the United States are considered obese. Hospitalized children who are obese are at increased risk for infection, prolonged lengths of stay and even death [3]. Other parameters that can be used to assess a child’s overall nutrition include nutrient intake compared to energy needs, weight gain velocity, mid-upper arm circumference and hand grip strength [4].

Children are frequently malnourished when in the hospital, although the specific incidence of malnutrition in hospitalized children in the United States is difficult to ascertain given the lack of consensus on how to assess nutritional status. One study from a large children’s hospital performed a single day cross sectional survey regarding in hospital malnutrition using clinical nutrition assessment, laboratory results and anthropometric measurements. They found that approximately 17% of the children were mildly malnourished, 6% were moderately malnourished and 1% were severely malnourished [5]. With regard to chronic malnutrition (assessing height for age), 15% were mildly malnourished, 8% moderately malnourished and 5% severely malnourished.

Several other studies have reported the incidence of acute malnutrition in hospitalized children to be between 6 and 30% (defined as weight for height less than two standard deviations below the mean) [6][7][8][9][10]. The incidence of malnutrition in children in the intensive care unit is significantly higher and estimated to be close to 30% [11].

Basic Science

What is the expected growth in premature and full term newborns and children?

Preterm infants between 24 and 30 weeks of gestational age should gain approximately 12 to 25 g/day, and from 30 weeks to full term approximately 25 to 35 g/day. Term infants gain an average of 25 to 30 g/day for the first three months of life and then 12 to 20 g/day between three and six months of age. In general, a baby will double his or her birth weight by the age of four to five months and triple their birth weight by twelve months. Body length is expected to increase by approximately 0.10 to 0.15 cm/day from birth to three months and from 0.04 0.075 cm/day until the first birthday. In general, a baby’s length will increase by 50% of birth length by the end of the first year [12].

What body composition and energy stores do the premature and full term neonate, child and adolescent have?

The body composition of premature babies is approximately 80% water, 11% protein, 8% fat and 2% minerals. By full term, the water composition decreases to approximately 75% with an increase primarily in fat (11%). By the first birthday, the body is approximately 60% water, 15% protein and about 20% fat; this ratio is more or less maintained into adulthood with some variation based on gender and overall fitness level [13].

In the first few hours of life, newborns rely on their own endogenous energy stores. Stored glucose in the form of glycogen can be accessed from the liver, kidneys and muscle. Premature babies have less reserve than full term infants due to their high water content. A baby weighing 1 kg has only approximately four days of nutritional reserve [13] compared to a full term infant who has enough stored glucose to support energy needs for approximately 12 to 24 hours and sufficient fat stores for about three weeks. Adolescents and adults have sufficient stores to survive approximately three days without water and three weeks without nutrition.

Energy Balance

How does the body maintain energy balance?

When food is catabolized it becomes oxidized to water, carbon dioxide, and/or urea and ammonia. During oxidation, energy is liberated and used to make high energy intermediates (mostly ATP and creatine phosphate). High energy phosphate bonds are then hydrolyzed as needed to release the stored energy. Each gram of fat catabolized stores 9 kcal of energy, compared to approximately 4 kcal for each gram of protein or glucose. The respiratory quotient (RQ) is used to estimate substrate oxidation and is the ratio of carbon dioxide production to oxygen consumption. In a fasting state, the RQ ranges from 0.7-1.0. An RQ significantly greater than one is seen during lipogenesis and is an indicator of excess caloric intake [14]. (see Medical Decision Making)

What are the nutritional needs of newborns, infants and children?

In utero, the fetus uses carbohydrates for the majority of its energy needs (80%). However, this changes shortly after birth when fat, a major component of breast milk, also becomes an important energy source. Energy and protein needs are the highest during the first few months of life and then gradually decrease until adolescence when there is another peak in energy requirements due to rapid growth. Unfortunately, definitive values for a particular patient’s energy requirements are difficult to determine because there are so many variables to consider. Energy needs vary with age, the overall health of the child, and activity level. Several formulas are used to determine baseline needs (basal metabolic rate (BMR) or resting energy expenditure (REE)). Traditionally, the Harris-Benedict equations for BMR have been used, but the Schofield equations are felt to be a more accurate measure of REE in children [15]. Unfortunately, neither of these formulas are predictive in the setting of critical illness [16] where children are often over- or underfed due to inaccurate estimations of caloric needs. There are also published estimates of recommended daily dietary intake available from the National Institutes of Health website regarding macro and micronutrients for children [17]. In general, newborn babies require 100 to 135 kcal/kg/d for normal growth with a breakdown of 2.5 to 3 g/kg of protein and 2 to 3 g/kg of fat per day. Older children should get approximately 30% of their calories from fat, 45 to 65% of calories from carbohydrate, and 10 to 20% from protein. (see Parenteral Nutritionfor estimates of daily caloric needs)

Energy Stores and Nutrition in the Neonate

How are the different energy stores used in the setting of illness, operation, or fasting?

Prenatally, the diet of the fetus is primarily glucose. After birth, when babies are breast fed, the calories from fat increase and the proportion from carbohydrate decreases. However, the brain can use only glucose or ketone bodies as energy sources, making euglycemia very important for neurodevelopment. During the third trimester, the fetus is able to take maternal glucose and store it as glycogen - primarily in the liver. These stores are then used in the first 24 hours of life. Gluconeogenesis, which occurs within the first four to six hours of life in term newborns, also provides a substrate for energy in the early newborn period [18].

Fat becomes an increasingly important energy source for babies - especially when fasting. Stored fat can be broken down to fatty acids and then oxidized to form ketone bodies (acetoacetate and beta-hydroxybutyrate) to fuel the brain if needed. By comparison, adults cannot use ketone bodies to fully substitute glucose as an energy source for the brain [19][20]. In neonates, fat is also important for maintaining a stable internal temperature. A full term baby must maintain a body temperature between 36 to 37º C. When an infant is stressed due to hypothermia, the first response is vasoconstriction followed by shivering to produce heat. Brown fat is the most important source of nonshivering heat production in neonates and makes up 90% of fat stores in newborns [21]. Interestingly, anesthesia inhibits the use of brown fat (non-shivering thermogenesis) and, therefore there is an increase in energy expenditure due to the need for thermogenesis at the end of surgery when the anesthetic is reversed, if the infant is exposed to cold [22].

Infants have very high rates of protein turnover (synthesis and breakdown) and are able to retain up to 80% of protein provided enterally or parenterally[23]. There are nine amino acids considered to be essential that cannot be synthesized in the human body (phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine) and in neonates, another five must also be provided by the diet (cysteine, taurine, tyrosine, glutamine, and arginine) [24]. Daily requirements are between 2.5 and 3.0 g/kg/d. Excess protein can result in azotemia, hyperammonemia and metabolic acidosis, but this is rarely seen when providing less than 3 g/kg/d. There are some groups of patients who have higher daily protein requirements (e.g. those with high ostomy losses) and, therefore, need to account for this in their nutritional intake. Increasing dietary protein enhances synthesis of protein, but the provision of fat and carbohydrate are also considered to be protein-sparing, thereby resulting in protein retention [25].

Why is euglycemia so important for the neonate?

It is well known that hypoglycemia in newborns should be avoided by keeping the blood glucose greater than 2.5 mmol/L (40 mg/dL) as a safe threshold for most babies [26].

Hyperglycemia can also be dangerous and should be avoided for babies in the long term. Extremely low birth weight infants who are receiving parenteral nutrition and/or corticosteroids for lung disease are the most susceptible to hyperglycemia, but it is often self-limiting. The initial approach to hyperglycemia is to decrease the glucose infusion rate and treat the underlying cause (pain, infection, etc.). There is an association between severe hyperglycemia (greater than 8.3 mmol/L) and increased mortality, as well as decreased white matter on brain magnetic resonance imaging [27]. There has been interest in using insulin infusions to achieve tight glycemic control in critically ill babies and children. Controversy remains regarding the benefit and safety of insulin infusion in this setting [28][29] and it is not currently the standard of care.

What is the significance of fats for the developing brain?

Long-chain polyunsaturated fatty acids (LC-PUFA), including docosahexaenoic acid (DHA) and arachidonic acid (AA), are found in breast milk and are believed to be important for human brain development. During infancy, there is significant accretion of both AA and DHA in the brain and more so in breast fed infants than in those who are formula fed. However, it is unclear whether supplementing formula with LC-PUFA results in improved cognitive outcomes [30]. One study looking at breast fed babies compared to those fed formula, either with or without LC-PUFA supplementation, found no significant difference in cognitive evaluation at three years of age [31]. Despite these data, it is still recommended that formulas be supplemented allowing for similar circulating levels of AA and DHA in both preterm and term babies.

Embryology

How does the placenta transfer glucose and other nutrients to the fetus?

The delivery of nutrients, carbohydates, protein, and lipids to the fetus is mediated by the placenta. Nutrients are received by the fetus via direct transfer from the maternal plasma to fetal plasma and through placental metabolism [32]. The fetus and placenta depend on glucose as the primary source of energy. The GLUT1 transporter is responsible for facilitative diffusion of glucose from the placenta to the fetus [33]. Amino acid transporters carry protein to the fetus as amino acids. Finally, lipids are delivered via lipoproteins and the direct transport of fatty acids. The placenta interacts with the fetus and modifies metabolism to affect the exchange of nutrients. For example, higher birth weight babies are associated with elevated maternal glucose.

Pathophysiology

What are the effects of the critically ill and postoperative catabolic stress state upon amino acid, carbohydrate, and lipid turnover and metabolism?

The metabolic stress response was originally described in terms of two phases [34]. The initial transient ebb phase is defined by depressed metabolism and is associated with reduced oxygen demands, low cardiac output, and decreased heat production. The subsequent hypermetabolic flow phase varies with the intensity and duration of injury. It is driven by increased cytokine production and is characterized by increased oxygen consumption, glucose production, and cardiac output.

In general, turnover and metabolism of amino acids, carbohydrates, and lipids are increased in the physiologically stressed child, as much as two- or three fold, depending on the duration of the illness or severity of the surgery or trauma. This adaptive response is initially beneficial as the increased availability of each of these building blocks can reduce or modify energy consumption, delay anabolism and activate a robust immune response. Prolonged stress, however, is of particular consequence in newborns whose endogenous glucose and protein stores are already quite low. Increased catabolism of muscle protein and the turnover of glucose leads to a loss of muscle mass, weight loss, delayed wound healing, and immune dysfunction. Fatty acid deficiency can result in thrombocytopenia, susceptibility to infection, dermatitis, and failure to thrive.

Protein turnover in metabolically stressed children may increase 80 to 100% above the already relatively high normal turnover rates necessary for growth and development (3.5 g/kg/day in adults versus 6 to 12 g/kg/day in newborns). Muscle protein catabolism leads to an increase in circulating amino acids. These are utilized for tissue repair, oxidation, ureagenesis, and protein synthesis. Amino acids also serve as mediators for an inflammatory response and, in the liver, are the substrate for gluconeogenesis. Supplemental protein slows, but does not halt the net negative protein balance associated with a hypercatabolic state. Tight glycemic control in critically ill children has been the focus of recent research, particularly in postoperative cardiac surgery [35]. A clear benefit from the standpoint of morbidity and mortality, along with safety, has not yet been consistently demonstrated.

What effect does the provision of glucose, lipid, and protein have upon turnover/metabolism in the critically ill and postoperative pediatric patient?

Although the provision of glucose, lipid, and proteins can avoid the need for the increased utilization of any one source of energy, they do not diminish the previously discussed increase in metabolism and turnover associated with the stress response.

Carbohydrates, given as monosaccharides, disaccharides, and complex carbohydrates can help prevent the breakdown of proteins into amino acids that would otherwise provide an immediate source of energy. In infants, whose glycogen reserves are normally low, inadequate provision of carbohydrates can lead to a ketotic state in less than 24 hours resulting in the utilization of fat and muscle as substrate for gluconeogenesis. Unbalanced or excessive administration of supplemental glucose in an attempt to mitigate the effects of increased utilization can potentiate hyperglycemia. This may lead to CO2 over-production, increased respiratory rate, and potential need for escalation of ventilatory support.

The provision of protein must include both the correct quantity and complement of amino acids appropriate for the changes in the amino acid profile associated with prematurity and stress. For example, cysteine and glutamine, while nonessential in healthy subjects, become essential amino acids in critically-ill children. The absence of even one of the amino acids can lead to a negative nitrogen balance.

Fatty acids are an important energy source in critically ill and stressed children. The provision of lipids can avoid the development of essential fatty acid deficiency which occurs after seven days of a fat-free nutritional regimen (or as soon as two days in preterm infants) [36]. Lipid added to parenteral nutrition can lead to decreased lipogenesis from glucose by improving nitrogen retention and utilization. This decreases the metabolic rate, oxygen consumption and carbon dioxide production [37].

What hormonal and cytokine profile is associated with the critically ill and postoperative catabolic state?

A spectrum of neurohormonal changes occur in critically ill and postoperative patients. Resistance to growth hormone develops in critically ill adults resulting in the disruption of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis [38]. The exact relationships of the factors related to this axis (Insulin-like Growth Factor Binding Protein-3, cortisol, and insulin) are the focus of recent basic science and translational research. A decrease in IGF-1 leading to an elevation of serum insulin has been observed in critically ill children and adults[39]. Glucagon, cortisol, and catecholamines are all catabolic hormones that are also elevated during illness.

Cytokines are an important component of the local and systemic response to stress, particularly in setting of sepsis, trauma, and burns [40]. They act via autocrine, paracrine, and endocrine communication, although they are not stored intracellularly. Their de novosythesis is largely controlled by the transcription factor NFκB. Proinflammatorycytokines associated with the stress response include TNF-α, IL-1α, IL-1β and IL-6. These may be beneficial as they delay anabolism, activate the immune response, and reduce metabolism. TNF-α is an important component of macrophage activation.

Presentation

What types of patients are at high risk for nutritional deficiencies?

Children in the intensive care unit who are critically-ill are at increased risk for nutritional deficiencies, as are those with congenital heart disease [41]. Other groups of patients with high fluid, electrolyte, and protein losses, such as those with short bowel syndrome and burns, are also at risk and should be screened routinely. The most common nutritional deficiencies in young children worldwide are iron and vitamin D deficiencies [42].

Assessment

What are the best ways to determine if a child is malnourished?

There are many parameters that can be used to determine a child’s nutritional status including their dietary intake, ability to meet predicted daily requirements, physical appearance (muscle wasting, edema, ascites), anthropometric measures (weight and height velocity, mid-upper arm circumference, handgrip strength, triceps skinfold thickness), and clinical status (sepsis, emesis, diarrhea). Standardized screening tools that incorporate both objective and subjective measures and that can be rapidly administered by both clinical and nonclinical individuals are commonly used. There are several different screening tools available online. The two that are commonly used include the Subjective Global Assessment (SGA), also called the Subjective Global Nutritional Assessment (SGNA) when used in children, and the Mini Nutrition Assessment (MNA).

The SGA is based on findings from the patient’s history and physical exam including changes in weight, dietary intake, functional capacity, gastrointestinal symptoms, loss of subcutaneous fat, ankle and/or sacral edema, etc. There is no explicit scoring system, but rather it is based on subjective interpretation. A score of one is given for none, two for moderate, and three for severe malnourishment. A recent study validated this tool in hospitalized pediatric patients [43], although, ultimately, the success of the assessment hinges on the experience of the person who is administering it.

The MNA provides a rapid assessment of nutritional status and has been validated in adults. The aim is to identify patients who would benefit from nutritional intervention. It includes anthropometric measures, questions related to lifestyle and mobility, dietary questions, and subjective assessment [44].

Additional screening tools for children include STAMP (Screening Tool for the Assessment of Malnutrition in Pediatrics) and STRONGkids (Screening Tool Risk on Nutritional Status and Growth). A recent meta-analysis did not find one tool to be superior to the other with regard to accuracy in detecting malnourishment [45]. It is important to remember that obese children also need to be screened for malnutrition. These patients can have micronutrient deficiencies, chronic inflammation, and decreased muscle mass.

Please see Additional Resources for links to growth charts and anthropometric measures.

How do you estimate or measure resting energy expenditure in the critically ill or postoperative pediatric patient?

The energy needs of children, ranging from hypermetabolic to hypometabolic, change frequently during the course of an illness and depend on factors such as mechanical ventilation, trauma, infection, open wounds, burns, edema, ascites, and/or malnutrition [46]. For example, infants seem to have increased energy requirements when they are septic, but only a very short term increase in needs after they have had surgery [47][48][49].

The use of indirect calorimetry to determine caloric needs is preferred over standard equations (e.g. Schofield equations) to provide a more accurate assessment [50]. Indirect calorimetry involves measuring expired gases to determine oxygen consumption (VO2) and carbon dioxide production (VCO2). In order to do this it is necessary to know the amount of inspired oxygen the patient is receiving, and the expired gases need to be isolated. if the patient is being mechanically ventilated, the calorimetry module can be incorporated directly into the ventilator. If the patient is breathing independently, a metabolic cart can be brought to the patient’s room and a hood canopy system can be sued to capture expired gases. This allows for the calculation of the resting energy expenditure (REE). REE can be calculated with the following equation: REE = (3.94 X VO2) + (1.06 X VCO2) - (2.17 X urinary urea nitrogen excretion). Ideally, the patient should reach a steady state, without extra movements and/or agitation, for about thirty minutes prior to taking the measurements, analgesia and anxiolytics should be given if needed to control pain and anxiety [51]. Indirect calorimetry is particularly useful in patients with an altered REE (e.g. trauma, severe sepsis, obesity, renal failure, paralysis) or when it is difficult to reach nutritional goals despite what appears to be sufficient nutritional support.

How does total energy expenditure vary as a function of age?

When determining a child’stotal energy expenditure (TEE), in addition to the basal metabolic rate (BME) one must consider the energy used for growth, activity, and digestion of food. This is important because energy expenditure can vary depending on a child’s age and overall well-being. For example, babies who are receiving an elemental formula do not require as much energy for digestion compared to those receiving more complex nutrition [14]. Additionally, premature babies grow at a more rapid rate (17 to 19 g/kg/d) than full term infants (4 to 8 g/kg/d) and, therefore, require more energy for growth [52]. Older children and adults use very little energy for growth, but can have considerably higher energy requirements for daily activities.

How is nitrogen balance assessed in the critically ill and post-operative pediatric patient and what are the implications of the nitrogen balance?

Nitrogen is a significant component of amino acids and the nitrogen balance can be used to quantify protein metabolism. Urea is the main excretory product of nitrogen breakdown and is mostly found in urine and sweat. Nitrogen balance is calculated by subtracting nitrogen losses (24 hour urine urea nitrogen and other nitrogen losses which usually range from 5 to 12 mg/kg/day) from the total nitrogen intake (24 hour dietary protein intake where 1 g nitrogen = 6.25g protein). There are several online calculators to assist with this calculation [53]. Children should be in a positive nitrogen balance due to active growth, whereas adults are in nitrogen equilibrium. A positive balance indicates sufficient protein and energy intake, whereas a negative balance suggests protein breakdown or inadequate protein or caloric intake. There is some evidence that branched chain amino acids can stimulate protein synthesis and decrease catabolism [54]: they have been given to critically ill children to improve nitrogen balance [55].

What laboratory tests are helpful in assessing nutrition?

Certain laboratory values can provide insight into a child’s overall protein status. Albumin is often monitored because it is the most abundant protein in the blood. Unfortunately, serum levels can be maintained within the normal range despite malnutrition because of its prolonged half-life (twenty days). It is, therefore, not a very sensitivity marker. However, hypoalbuminemia (less than 3.5 g/dL) is a reasonable marker of morbidity and mortality in children.

In contrast, prealbumin, transferrin, and retinol binding protein have short half lives of only two days, seven days and twelve hours, respectively. They are better markers of visceral protein status. Lastly, a complete blood count with differential is the most economical measure of nutritional status since lymphopenia is a known feature of protein energy malnutrition, although it is both nonspecific and insensitive.

Medical Treatment

Enteral Nutrition

What are the different types of enteral formulas and how does one decide which to use?

Human milk is the preferred nutrition in the first year of life. Donated expressed breast milk (EBM) can be used when the mother cannot produce sufficient volume. EBM confers immunologic protection and may decrease the risks for necrotizing enterocolitis compared to infant formula. Infants who are exclusively breast milk fed require 1 mL/day of liquid multivitamin.

The nutrient composition of most infant formulas simulates maternal milk: protein 8 to 12%, carbohydrates 41 to 43%, and fat 41 to 49%. Docosahexaenoic acid and arachidonic acid are added for brain and retinal development. Iron is added to meet the 2 to 4 mg/kg/day requirements. Enfamil®, Similac®, and Good Start® are made from bovine milk. Isomil® and Prosobee®, based on soy protein and corn syrup, can be used in infants with lactose or milk protein intolerance. Pregestimil® and Alimentum® are made with hydrolyzed bovine protein and are thought to benefit patients with suboptimal digestion and absorption such as short bowel syndrome, malabsorption, cystic fibrosis and biliary atresia. Pregestimil® and Portagen® are formulas with the highest percentage of medium chain triglycerides and, because of direct diffusion into the portal system, are used in children with fatty acid malabsorption. Neocate® and Elecare® are elemental formulas and are used in patients with severe bovine protein allergies and those with other digestive problems in whom nutrition has failed on Pregestimil® and Alimentum®.

Premature infant formulas are indicated for preterm infants with birth weights less than 1800 g. Similac Special Care® and EnfamilPremature® are available in 20, 24 and 30 kcal/ounce formulations.

Human Milk Fortifier (HMF) is a bovine milk based powder that can be added to EBM to increase caloric density. One packet adds 2 kcal/oz when added to 50 mL of EBM. Prolacta is a fortifier concentrated from donor human milk available in four preparations which can raise the caloric content of EBM by four, six, eight and ten calories per ounce.

SimilacPM® 60/40, used in renal failure patients, has the same amount of protein as term infant formula (whey:casein content of 60:40), the same mineral content as human milk and less sodium, potassium and phosphate than term infant formulas.

Carbohydrate free formulas are indicated in patients who have disorders of carbohydrate absorption, such as disaccharidase deficiencies. Diet powder 3232A, which is free of monosaccharides and disaccharides, is a bovine milk protein hydrolysate with medium chain triglyceride (MCT) oil and minimal carbohydrate. RCF is a soy product with protein and fat, but minimal carbohydrate, and is used in infants who require a ketogenic diet.

The caloric density of pediatric formulas range from 1 to 1.5 kcal/ml. Pediasure® is lactose free. PeptamenJr® is 100% hydrolyzed whey and 60% of the fat is provided as MCT oil (toddler equivalent of Pregestimil®). Elecare® is amino acid-based, lactose-free, has 33% MCT oil and has an oral formulation that is vanilla flavored. Neocate Jr.® and Vivonex® are also alternative elemental formulas. Nutritional supplementation can be accomplished by adding Duocal® (fat and carbohydrates, 42 kcal/tbsp), vegetable oil, medium chain fat emulsions, Beneprotein® or Benefiber® as needed [56].

Infant formulas [57]

Formula

kcal/mL

Protein (g/L)

Protein (%kcal)

Protein source

CHO Source

CHO (%kcal)

Fat Source

Fat (%kcal)

Indications

Similac Special Care® (Abbott Nutrition)

0.81

24

12

Nonfat milk, whey

Lactose, corn syrup solids

41

MCT oil, soy oil, coconut oil

47

Prematurity

NeoSure® (Abbott Nutrition)

0.73

21

11

Nonfat milk, whey

Lactose, corn syrup solids

42

MCT oil, soy oil, coconut oil

48

Prematurity, discharge formula

Enfamil® (Mead Johnson)

0.67

14

8.5

Whey, nonfat milk

Lactose

43.5

Palm olein, soy oil, coconut oil, sun oil

48

Standard

Similac® (Abbott Nutrition)

0.67

14

8

Nonfat milk, whey

Lactose

43

Soy oil, coconut oil, safflower oil

49

Standard

0.81

17

8

Nonfat milk, whey

Lactose

43

Soy oil, coconut oil, safflower oil

49

ProSobee® (Mead Johnson)

0.67

17

10

Soy isolate, methionine

Corn syrup solids

42

Palm olein, soy oil, coconut oil, sun oil

48

Lactose intolerance, galactosemia

Isomil® (Abbott Nutrition)

0.67

17

10

Soy isolate, methionine

Corn syrup, sucrose

41

Soy oil, coconut oil, safflower oil

49

Lactose malabsorption, galactosemia

Nutramigen® (Mead Johnson)

0.67

19

11

Casein hydrolysate, cystine, tyrosine, tryptophan

Corn syrup solids, modified cornstarch

41

Palm olein, soy oil, coconut oil, sun oil

48

Protein intolerance

Pregestimil® (Mead Johnson)

0.67

19

11

Casein hydrolysate, cystine, tyrosine, tryptophan

Corn syrup solids, modified cornstarch, dextrose

41

MCT oil, corn oil, soy oil, safflower oil

48

Protein intolerance, cystic fibrosis, neonatal cholestasis, short bowel syndrome

Alimentum® (Abbott Nutrition)

0.67

19

11

Casein hydrolysate, cystine, tyrosine, tryptophan

Sucrose, modified tapioca, starch

41

MCT oil, safflower oil, soy oil

48

Protein intolerance, neonatal cholestasis

Neocate® (Nutricia North America)

0.67

21

12

Free amino acids

Corn syrup solids

47

MCT oil, safflower oil, corn oil, soy oil, sun oil

41

Food allergy, protein intolerance, short bowel syndrome

EnfaportLipil® (Mead Johnson)

1

35

14

Calcium caseinate, sodium caseinate

Corn syrup solids

41

MCT oil (84%), soy oil

45

Chylothorax, LCHAD deficiency

CHO - carbohydrate, LCHAD - long chain 3-hydroxyacyl-CoA dehydrogenase

Pediatric formulas [57]

Formula

kcal/mL

Protein (g/L)

Protein (%kcal)

Protein Source

CHO Source

CHO (%kcal)

Fat Source

Fat (%kcal)

Indications

PediaSure® (Abbott Nutrition)

1

30

12

Milk protein concentrate, whey protein, soy isolate

Corn maltodextrin, sucrose

53

Safflower oil, soy oil, MCT oil

35

Standard, oral feeds, tube feeds

Boost® (Mead Johnson)

1

42

17

Milk

Corn syrup, sucrose

68

Canola oil, corn oil, sunflower oil

15

Standard, oral feeds, tube feeds

PeptamenJunior® (Nestle Nutrition)

1

30

12

Hydrolyzed whey

Maltodextrin

55

MCT, soy oil, canloa oil

33

Short bowel syndrome, cholestasis, pancreatitis

L-Emental® (Hormel Health labs/Nutrition Medical)

0.8

40

16

l-amino acids

Maltodextrin, modified starch

82

Safflower oil

2

Short bowel syndrome, inflammatory bowel disease, pancreatitis

EleCare® (Abbott Nutrition)

0.67

21

15

l-amino acids

Corn syrup solids

43

MCT, safflower oil, soy oil

42

Malabsorption, food allergies

Suplena® (Abbott Nutrition)

1.8

45

10

Sodium caseinate, milk protein isolate

Corn maltodextrin, sucrose

51

Safflower oil, soy oil, canola oil

48

Renal failure

CHO - carbohydrate

How quickly should enteral nutrition be started and advanced in the critically ill and postoperative patient?

Multiple published guidelines support the provision of early enteral feeding in patients who are unable to maintain adequate oral intake in the first week of admission to an intensive care unit [58][59][60]. Although adult patients and older children can tolerate fasts of five to seven days, smaller children and infants have less nutritional reserve and require the initiation of enteral nutrition in as little as 48 hours. Even 24 hours of fasting can lead to hypoglycemia in the newborn. Failure to maintain adequate enteral nutrition is most often secondary to interruptions in feeding schedules due to procedures, fluid restrictions, and intolerance of feeds. Improved mortality and reduced pneumonia and sepsis rates have been associated with the initiation of early enteral nutrition - defined as within the first 24 to 48 hours.

Term newborns require 100 to 120 cal/kg/day for normal growth with an ideal weight gain goal of 20 to 30 g/day. Extremely low-birth-weight preterm newborns require 130 to 150 cal/kg/day for normal growth with an ideal weight gain goal of 15 to 20 g/kg/day. Ideally, infants should achieve a one percent increase in weight per day.

Should enteral nutrition be administered in the stomach or jejunum and by bolus or continuous administration?

Evidence does not clearly support one method of administration of enteral nutrition. Intuitively, although gastric bolus feeds best emulate normal physiologic conditions, patients unable to tolerate gastric feeds or at high risk for aspiration should be fed via a postpyloric approach. Randomized trials, however, have had conflicting results.

Multiple studies in adults and children have been unable to demonstrate a difference in rates of vomiting, aspiration, or pneumonia when comparing patients fed into the stomach versus the small bowel [61][62][63]. Additionally, more rapid achievement of nutritional goals has been demonstrated in some studies through a gastric-fed approach, while others support small bowel feedings. Several studies have failed to demonstrate a difference in stooling patterns as a marker of effectiveness of continuous versus bolus feeds in very low birth weight infants. A recent large meta-analysis found a reduced pneumonia rate in postpyloric-fed, critically-ill adults, but no evidence to support improved outcomes in terms of duration of mechanical ventilation, length of stay, or mortality[61]. It did, however, support placement of postpyloric tubes as a safe procedure. One challenge in the provision of jejunal feeds is the placement of a postpyloric tube as this can delay the initiation of feeds. Many successful fluoroscopic, endoscopic or magnetic techniques to place postpyloric tubes have been described.

How often is enteral nutrition effective in meeting the caloric goals of critically ill children?

Several studies have demonstrated that in septic or critically-ill intensive care unit patients, only 25 to 50% met nutritional goals [11][64]. Unmet nutritional needs are often the result of interrupted feeding schedules (relating to NPO status for procedures), fluid restrictions (particularly following cardiac surgery) and feeding intolerance.

Is there evidence to support fast track pathways for enteral nutrition in children?

Multiple recent studies have demonstrated that feeding protocols can assist in optimizing nutrition in critically ill children [65][66][67][68]. The benefits of these protocols include more rapid initiation of nutritional support, a higher rate of enteral feeding, and a higher proportion of patients reaching half or more of their recommended intake [68]. Regular audits of pathways help support institutional commitment and adherence, which is at least partially responsible for the beneficial effects observed. Protocols include guidelines on timing to initiation, route, rate, type, and advancement plan of enteral feeds. Some institutional protocols have expanded to include the parenteral route as part of a nutritional support algorithm.

gastric feeding protocol

Sample gastric feeding protocol for patients aged 1-6 years. (from Meyer et al, Journal of Human Nutrition and Dietetics, 22: 428-436, 2009.
http://onlinelibrary.wiley.com…)

jejunal feeding protocol

Sample nasojejunal feeding protocol for patients 1-6 years (from Meyer et al, Journal of Human Nutrition and Dietetics, 22: 428-436, 2009.
http://onlinelibrary.wiley.com…)

Parenteral Nutrition

What factors lead to the consideration to start total parenteral nutrition in the critically ill and postoperative patient?

Parenteral nutrition (PN) is a lifesaving modality for patients who are unable to tolerate adequate enteral nutrition [69]. Premature infants require slow progression of feeding to allow tolerance and prevent necrotizing enterocolitis. Early initiation of parenteral nutrition is indicated for sick or premature infants because of the additional requirements for development and growth. Older children and adults may develop significant morbidity if starvation exceeds five to seven days - especially patients with head injuries or burns who may be hypermetabolic. Extra low birth weight infants may develop essential fatty acid deficiencies in only three days. Other indications for parenteral nutrition include short bowel syndrome, radiation enteritis, intractable vomiting and diarrhea, severe acute pancreatitis, and high output enterocutaneous fistulae[56].

What is the optimal glucose infusion rate in stable newborns?

Stable preterm newborns should receive 5 to 7 mg/kg/min of carbohydrate, while term infants should receive 6 to 9 mg/kg/min. This should be given as 5 or 10% dextrose concentration. The rate (mg/kg/min) may be calculated with the following equation:

[IV rate (ml/hr) * Dextrose Concentration (g/dL) * 1000 (mg/g)] / [weight (kg) * 60 (min/hr) * 100 mL/dL)

Several on line calculators can be used to determine the optimal rate based on the infants weight and concentration of dextrose being infused.

When is peripheral parenteral nutrition appropriate and how does it differ from centrally administered parenteral nutrition?

Parenteral nutrition can be administered peripherally for any patient who needs transient supplementation for enteral nutrition due to a brief period of starvation or inadequate caloric intake. Parenteral nutrition administered peripherally must be diluted to avoid osmotic injury to the vein. The dilution of the formulation reduces the amount of nutrition that can be delivered, although isotonic lipids can provide a substantial amount of nonprotein calories. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) recommends in its guidelines that the maximal allowable osmolarity of the infusate is 900 mOsm/L [70]. Although a more concentrated formulation may be tolerated, the evidence for the safety of any higher concentration peripherally is lacking [71].

The primary benefit of peripheral PN is the avoidance of the placement of a central venous catheter. The placement of central lines may lead to iatrogenic injury, including injury to adjacent vascular or central structures (e.g. pneumothorax), introduction of air or thrombotic embolus, misplacement leading to contrast extravasation, and possible intra-abdominal or intra-thoracic infusions of parenteral nutrition. Once in place, the line itself can be an entry or nidus for infection leading to bacteremia, fungemia, or sepsis. Long term catheters are associated with pericatheter thrombus formation or venous stenosis.

How do you initiate parenteral nutrition?

Glucose is an essential fuel source - especially for brain metabolism. Sick infants should be monitored closely as their glucose levels may fall rapidly and a glucose infusion should be initiated. Infants who are preterm or growth restricted or who have experienced placental insufficiency often have low liver glycogen stores and may fail to maintain adequate serum glucose levels. Infants of diabetic mothers are also at risk for hypoglycemia because high levels of maternal blood glucose cross the placenta causing fetal hyperinsulinemia which persists after birth. For any blood glucose less than 40 mg/dL, an infusion of dextrose should be initiated. Symptomatic hypoglycemia should be treated with a 2 mL/kg bolus of D10W followed by a continuous glucose infusion. Glucose levels should then be checked at thirty minute intervals with continued surveillance until stabilization. Insulin resistance and hyperglycemia may occur in septic patients or extremely premature infants.

The initial PN glucose infusion rate for infants should be 4 to 6 mg/kg/minute advancing 2 mg/kg/minute each day as long as the serum glucose remains less than 150 mg/dL to the maximum of 12 to 14 mg/kg/minute. Exceeding the upper limit of 14 mg/kg/minute may result in overfeeding and fatty infiltration of the liver [69]. In addition, over reliance on glucose causes excessive CO2 production which theoretically could be detrimental to patients with compromised ventilatory function.

Fat is generally required for skin integrity, but especially for the growth, development, and proper function of the brain. Lipid infusions provide significant calories, but are most important because they prevent essential fatty acid deficiency syndromes. Neonates, especially premature infants, can develop this problem within a few days of life without the provision of fatty acids. The syndrome is characterized by dry skin, defective wound healing and respiratory distress. Provision of 5 to 8% of total calories as lipid is preventative.

The initiation of fat emulsion (Intralipid) should begin slowly in infants with 1 g/kg/day for those less than 2 kg or 2 g/kg/day for patients who are over 2 kg. Advancement in lipids should be 0.5 to 1 g/kg/day while simultaneously monitoring serum triglyceride levels to keep levels below 150 to 200 mg/dL. The maximum dose in infants and children is 4 grams/kg/day and 2 grams/kg/day in adults. Higher doses may have deleterious effects on reticuloendothelial and pulmonary function. Protein should be started at 2.5 g/kg/day and advanced by 1 g/kg/day to a maximum of 4 g/kg/day for preterm infants, 3 g/kg/day for term infants and 1 to 2.5 g/kg/day for children and adults.[56]

The most commonly utilized intravenous solution for lipid administration in the United States is Intralipid® made from soybean oil. Both the 10% and the 20% solutions of Intralipid® contain 1.2% egg yolk phospholipids and 2.25% glycerin. The 20% emulsion is preferred for infants because of the lower proportion of phospholipids relative to calories. Omegaven® 10% is a fish oil emulsion with an omega 6 to omega 3 ratio of 1:7 which has been used to treat parenteral nutrition associated liver disease [72] (see Complications). This product is not currently available commercially in the United States.

Protein requirements in postoperative or stressed patients are increased due to accelerated visceral and somatic protein catabolism and decreased extrahepatic protein synthesis. Two commercial preparations of crystalline amino acids are commonly available. TrophAmine® (10%) includes all essential amino acids except for l-cysteine. (see Basic Science) It contains taurine which is a conditionally essential amino acid in growing infants. When TrophAmine® is used, l-cysteine is added as an additional component at a dose of 40 mg/gram of protein delivered. Typically, TrophAmine® is used in newborns less than three months of age. Travasol® was designed for adults, but will meet the protein needs of children greater than three months of age.

The branched chain amino acids (valine, leucine, isoleucine) are the main amino acids available in PN solutions. Aromatic amino acids (e.g., phenylalanine) should be avoided in liver disease. In renal failure, only essential amino acids are given in order to avoid excessive production of renally excreted urea from nonessential amino acid nitrogen sources. Arginine supports immune function (T-cells) and also stimulates insulin production, which is anabolic.

Both calcium and phosphorus are essential for skeletal development and maintenance. Premature infants are deficient in both. Potential precipitation of calcium with anions requires careful adjustment in parenteral nutrition. The calcium to phosphorus ratio should be optimized to provide for bone development and health. A 1:1 ratio of 2 mEq/kg/day of calcium to 2 mM/kg/day of phosphorus is ideal, but ratios can range from 0.5:1 to 2:1. Calcium intake recommendations are 1 to 3 mEq/kg/day for maintenance and 3 to 5 mEq/kg/day for growth. Phosphorus intake recommendations are 1.3 mM/kg/day for maintenance and 2 mM/kg/day for growth. Hypocalcemia is common in premature infants, asphyxiated infants, infants of diabetic mothers, and infants of hypoparathyroid mothers. Symptoms include irritability, jitteriness, and seizures. Symptomatic or extremely low birth weight infants should have early supplementation. Central venous access is preferred because of soft tissue injuries that can occur with peripheral venous infiltration.

Magnesium is an essential component in maintaining calcium homeostasis and levels should be monitored closely during the initiation of parenteral nutrition. Daily doses of 0.5 to 1 mEq/kg/day of magnesium should be administered.

Acetate is an anion that does not precipitate with calcium and, therefore, helps to balance the metabolic acidosis that may occur with PN chloride administration. Acetate is especially important in the preterm neonate who normally excretes excess bicarbonate. Whenever acetate in PN is used to treat metabolic acidosis, the cause of the metabolic acidosis must be identified.

Trace elements and multivitamins are also required and should be part of a parenteral nutrition formulation.

Additional medications may be provided as part of parenteral nutrition. Heparin may be added in small amounts to help maintain patency of central lines.

Initiation of parenteral nutrition should begin with 25 to 30 kcal/kg/day with advancement over several days to reach goal calories. Adults and adolescents usually receive 35 kcal/kg/day. Term infants should receive 80 to 100 kcal/kg/day and preterm infants at least 90 to 110 kcal/kg/day. Goals for weight gain are 20 g/kg/day for infants less than 37 weeks gestational age and 30 g/kg/day patients for infants greater than 37 weeks gestational age.

When should one discontinue parenteral nutrition?

The adequacy of nutritional support is best estimated based on observed weight gain and serial observations on standard growth charts. PN should be decreased as enteral nutrition is tolerated. The amino acid and lipid portions of parenteral nutrition can be stopped when the enteral route tolerates 50% of the total nutrition.

To avoid rebound hypoglycemia when cycling PN off, tapering should occur over one to two hours where the PN is run at 50% for thirty to sixty minutes and then at 25% for another thirty to sixty minutes.

What monitoring is required during initiation and maintenance of parenteral nutrition?

Laboratory monitoring of patients on PN should initially include daily electrolytes, magnesium, phosphorous, and ionized calcium. Serum triglycerides should be checked with each increase in lipids. After a few days of stable values these items are checked twice a week. Liver enzymes, bilirubin, alkaline phosphatase, and a complete blood count are checked every other week.

What are the individual glucose, protein, and lipid targets for TPN and how are the quantities of these nutrients calculated?

a) Calculate maintenance fluid requirements using ideal body weight: 4 ml/kg for the first 10 kg, 2 ml/kg for second 10 kg, then 1 ml/kg for greater than 20 kg.

b) Calculate daily caloric needs: 100 kcal/kg for the first 10 kg, 50 kcal/kg for the second 10 kg, and 20 kcal/kg for each kg greater than 20 kg.

c) Caloric distribution: 30 to 40% from fat, 50 to 60% from carbohydrates, and 8 to 12% from protein.

i) Calculate daily protein calories

(1) Protein Calories = 2 to 4 g protein/kg x 4 kcal/g protein

ii) Calculate daily fat calories

(1) Fat Calories = 0.3 to 0.4 x total calories

(2) 20% fat emulsion has a caloric density of 2.2 kcal/ml

(3) Fat calories/2.2 = mL of 20% Intralipid

iii) Calculate Carbohydrate calories

(1) Carbohydrate calories = Total Caloric Needs - [Fat Calories + Protein Calories]

(2) Caloric Density of parenteral dextrose is 3.4 kcal/gram

(3) Carbohydrate calories x 1 gram/3.4 kcal = grams dextrose needed

(4) Usually start at D10 (infants) or D12.5 for older children

(5) Dextrose infusion rate (mg/kg/min) = [0.69 x Dextrose% x 24 x rate (ml/hr)]/body weight (kg)

What vitamins and trace elements are required in the patient receiving enteral nutrition or parenteral nutrition?

The trace elements that are required for growth and metabolism are in such small amounts that individual supplementation is not feasible. The trace elements solution is usually given as 0.15 mL/kg/day and consists of manganese 3.75 mcg, chromium 0.15 mcg, copper 15 mcg, and selenium 2.25 mcg. Chromium and selenium undergo renal excretion and, therefore, should be used cautiously in patients with renal failure. Manganese and copper should be decreased in patients with liver compromise due to impaired biliary excretion. Ceruloplasmin levels should be checked two weeks after alterations of copper in parenteral nutrition.

Zinc is essential for growth and the normal function of skin and the intestine. Premature infants should receive 400 mcg/kg/day. Term infants who weigh more than three kilograms should receive 50 to 250 mcg/kg/day, and children who are greater than 10 kg should receive 50 to 125 100 mcg/kg/day.[73] In patients with high volume gastrointestinal losses from stomas or diarrhea, the administration of more than 400 mcg/kg/day may be needed regardless of the patients’ age. Trace elements are essential: Deficits of zinc cause acrodermatitis enteropathica, which is characterized by dermatitis, glossitis, alopecia and diarrhea. Chromium deficits produce hyperglycemia. Copper deficits may present as an anemia that is not responsive to iron administration.

Carnitine is a cofactor for the transport of long-chain fatty acids into mitochondria and some studies suggest that it is an essential cofactor in infancy. Premature infants can develop a deficiency of carnitine stores within one week. L-Carnitine at 5-10 mg/kg/day should be added to the parenteral nutrition in neonates.

Multivitamins should be provided on a daily basis by weight (see table). These should include the fat soluble vitamins (A, D, E, and K), as well as the water soluble vitamins (ascorbic acid, B12, biotin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamine).

Weight based multivitamin administration

Weight (kg)

Multivitamin volume (mls)

1

1

1 to 1.5

2

1.5 to 2

3

2.5 to 5

4

greater than 5

5

Medical Decision Making

What are the advantages of enteral over parenteral nutrition?

The proposed nutritional benefit of early initiation of feeds includes mitigating the metabolic stress response by the provision of adequate protein and calories. The nonnutritional benefits of early enteral feeds can be divided into gastrointestinal, immune, and metabolic aspects. The gastrointestinal responses to feeds include maintenance of gut mucosal integrity, prevention of bacterial translocation, and avoidance of gut mucosal atrophy all of which lead to enhanced gut motility, improved absorptive capacity, support of commensal bacteria, production of secretory IgA, and a trophic effect on epithelial cells. Immune responses include modulation of key regulatory cells that enhance systemic immunity; promotion of the Th-2 (anti-inflammatory) over Th-1 (proinflammatory) responses; influence of duodenal, vagal and colonic anti-inflammatory butyrate nutrient receptors; and maintenance of mucosa-associated lymph tissue. The metabolic benefits of enteral nutrition have been discussed in a separate section (see Pathophysiology) and include an attenuated metabolic stress response, enhanced nitrogen balance, reduced muscle and tissue loss, reduced incidence of hyperglycemia, and improved insulin sensitivity.

What factors affect a patient’s respiratory quotient?

The respiratory quotient (RQ) is defined as the ratio of the volume of CO2 production to the volume of O2 consumed. These values can be obtained by indirect calorimetry. The RQ values for various substrates are known: fat 0.7, protein 0.9, and carbohydrate 1.0. In general, the RQ is between 0.7 and 1.0 unless lipogenesis occurs due to overfeeding, at which point the RQ may be greater 1.0. A patient’s RQ will reflect the mixture of metabolized substrates and the tendencies toward 0.7 or 1.0 will indicate whether metabolism is predominantly lipid- or carbohydrate-based, respectively. As a result, the RQ can be used clinically to determine the primary fuel source and feeding status for a patient.

The implications of a predominantly carbohydrate source of metabolism or overfeeding include overproduction of CO2 which can compromise ventilator weaning. In fact, respiratory requirements may be lessened by increasing the relative proportion of fats in the diet and by reducing excess caloric intake. It is worthwhile to note, however, that hypertriglyceridemia may lead to fat deposition and a fatty liver.

While some recent studies have supported the use of hypocaloric feeding (relative starvation) with an increased provision of protein [74][75][76][77], a recent meta-analysis of adult patients showed no differences in mortality, infectious complications, intensive care unit admission days or ventilator-free days in patients maintained with permissive underfeeding [78]. Similar studies in pediatric patients are lacking.

What is the benefit of tight glucose control in the pediatric patient?

Hyperglycemia associated with a stress response may be transiently beneficial as it provides the host with an immediate substrate for metabolism. The deleterious physiologic effects of hyperglycemia include increased oxidative injury, an exaggerated proinflammatory response, coagulopathy, and immune dysregulation. These can all lead to sepsis and multi-organ dysfunction (particularly cardiac and renal). Tight glucose control, therefore, would ideally minimize the possibility of these effects. Biochemically, intensive insulin therapy has been shown to reduce multiple inflammatory markers [79] and a number of studies have demonstrated an adverse effect of prolonged hyperglycemia in critically-ill patients. One of the first randomized control trials of intensive insulin therapy in adults showed that maintaining blood glucose less than 110 mg/dL reduced morbidity and mortality in a surgical intensive care unit [80].

However, while multiple adult and pediatric studies (e.g.SPECs[81], NICE-SUGAR [82], CHiP[83]) have demonstrated a benefit to tight glucose control, an increase in the episodes of hypoglycemia associated with increased morbidity was also observed. A recent meta-analysis of 24 high quality manuscripts concluded that a strong recommendation could not be made in favor of tight glucose control in the pediatric intensive care unit [35].

How is parenteral nutrition adjusted in response to acid-base and other electrolyte derangements?

Serum electrolyte levels are followed for patients on PN and adjustments can be made in the formulation to correct for blood concentrations that are either too high or too low. In general, dramatic or time sensitive replacements should be done outside of the slowly infused PN and provided intravenously as riders or boluses, or as oral supplements if enteric intake will allow.

Two anions utilized in PN administration (chloride and acetate) can be used to affect the patient’s acid-base status. Excess chloride can lead to lower serum pH resulting in a metabolic acidosis. Excess acetate can result in metabolic alkalosis.

Preoperative Preparation

When should elective surgery be postponed secondary to malnutrition?

There are no published guidelines regarding strict criteria for the timing of surgery based on nutritional status. However, optimizing a child’s nutrition prior to surgery is important for achieving best outcomes. Malnutrition is an independent risk factor for complications in adults such as wound healing, increased length of hospital stay, and even mortality [84]. A recent study using the SGNA for screening children preoperatively before major abdominal or thoracic surgery found that malnourished children were more likely to have minor and infectious complications and a longer length of hospital stay [85]. However, the available literature supports the use of preoperative nutritional supplementation in the form of 7-10 days of enteral or parenteral nutrition, only for severely malnourished patients [86]. In general, there is a lack of prospective data correlating malnutrition in pediatric surgical patients with clinical outcomes making it difficult to make definitive recommendations [47]. There is some evidence to suggest that formulas enhanced with higher than normal levels of arginine, glutamine, nucleotides and omega-3 fatty acids can have anti-inflammatory, anabolic and tissue protective effects [87]. This has been termed immunonutrition (IMN) and several meta-analyses in adult patients have shown fewer complications and shorter length of stay with IMN[88] . However, the patients in these studies ranged in their degree of under nutrition and the applicability to chldren remains unclear.

With regard to patients who are obese, there is adult data to suggest that those with a body mass index greater than 40 have more postoperative infections and require more ventilatory support [89][90]. The obese patient should be screened for micronutrient deficiencies including vitamin D, B12, thiamine and iron with repletion as necessary [91][92]. Patients should ideally be placed on a hypocaloric (60 to 70% of expected needs), high protein diet (two g/kg ideal body weight) to promote weight loss through the reduction of fat mass [93].

Postoperative Care

Surgery results in a stress response in the body leading to the catabolism of glycogen, fat and protein to allow for appropriate healing. Measures to reduce the stress of surgery include maintaining a tighter fluid balance, providing adequate analgesia and reducing fasting periods to dampen the catabolic response [94]. As a result, although there is an immediate elevation in oxygen consumption and resting energy expenditure following major surgery, this is not sustained in the long term and metabolism essentially returns back to baseline within 12 to 24 hours [22][48]. Additionally, for infants, because less energy is used for daily activity and to maintain body temperature, postoperative caloric needs tend to be overestimated [95]. It is important to try to avoid providing excessive calories which can lead to hyperglycemia, lipogenesis and respiratory acidosis from increased carbon dioxide production [96].

Complications

What is the increased surgical morbidity for underweight or overweight patients?

Operating on malnourished patients, both underweight and overweight, continues to be a necessity for all pediatric surgeons. However, performing the appropriate preoperative risk assessment and discussing potential surgical risks with families is a challenge. Most published literature regarding surgical risk related to body mass index (BMI) includes only adults. A study in adults found that both underweight and morbidly obese patients had increased mortality after foregut surgery [97]. In a large study of adult surgical patients, those with a BMI less than 18.5 and greater than 40 had the highest thirty day morbidity and mortality from wound infections, respiratory complications, urinary tract infections, and cerebrovascular accidents. Interestingly, those with a BMI between 25 and 40 had the lowest morbidity and mortality [98]. Another large study found that obese patients had more intraoperative blood loss, longer operative times, and a higher risk of wound infection after general surgery procedures, but no affect on long term survival. In contrast, underweight patients demonstrated decreased survival [99]. There is a paucity of literature looking at BMI and outcomes after surgery in the pediatric population.

What are the potential complications of enteral nutrition?

Enteral nutrition is always the preferred mode for nutrient delivery and is encouraged as soon as there is evidence that the intestinal tract is functional. However, potential problems can arise from enteral feeding. Feeding intolerance in the form of diarrhea with malabsorption and/or emesis and abdominal cramping can occur if calories are delivered too quickly or at high concentrations. In the setting of feeding intolerance, a trial of continuous feeds at a slower rate and/or lower caloric concentration may be better tolerated. Patients should be monitored for the quantity and quality of stool output, including assessing for fat and/or carbohydrate malabsorption, when there is difficulty reaching fluid and caloric goals enterally.

What are the potential complications of parenteral nutrition?

Although parenteral nutrition (PN) is lifesaving for many patients, it is associated with significant risks. These risks include metabolic and infectious complications as well as the potential for hepatic cholestasis.

The most common metabolic disturbance during PN administration is hyperglycemia. This can lead to osmotic diuresis, dehydration, and may result in increased morbidity and mortality in extremely low birth weight infants [100]. Conversely, hypoglycemia can also be a problem if PN is stopped abruptly - especially in patients who are not receiving any enteral nutrition. (see Parenteral Nutrition)

Children receiving PN for prolonged periods of time are also at risk for metabolic bone disease. This is primarily due to the limitations in the amount of phosphorus and calcium that can be added to PN. In addition, aluminum is often a contaminant in PN and impairs calcium fixation in bones [101].

Infection is another major problem associated with the administration of PN and this is most commonly due to central line associated bloodstream infections (CLABSI). CLABSI result in significant morbidity to the patient and increased cost and length of stay [102]. The most effective strategies for decreasing the incidence of CLABSI have been initiating protocols for placing the catheters under sterile technique and for ongoing catheter care [103], including daily chlorhexidine baths [104]. According to the Clinical Practice Guidelines from the Infectious Diseases Society of America, catheters should be removed if the infection is secondary to S. aureus, P. aeruginosa, fungi or mycobacteria[105].

What are the causes of liver dysfunction during parenteral nutrition?

Hepatic cholestasis is another potential complication from prolonged PN use in children. This is particularly problematic in patients who are not receiving any nutrition enterally and who have short bowel syndrome or intestinal failure. Strategies to try to prevent cholestasis include avoidance of overfeeding, allowing for some time off PN each day, minimizing episodes of infection, and introducing enteral nutrition as soon as possible [106][107].

There are many factors that contribute to progressive hepatic cholestasis in children who are dependent on PN, with the components of the PN itself playing a major role. In general, the provision of excess calories, usually in the form of carbohydrate or fat, can result in lipogenesis and eventually steatosis [108]. All children who are receiving PN should also have their weight and other anthropometric measures carefully monitored to avoid excess weight gain. Although the role of specific amino acids in the development of cholestasis is less clear, there is some evidence to suggest that a deficiency of taurine and cysteine and an excess of methionine should be avoided [109][110]. In addition, manganese should be removed from PN if long term use is expected.

More recently there has been much emphasis on the type of lipid emulsion administered and the implications of certain fatty acids on the development of hepatic cholestasis and fibrosis. Commonly in the United States, intravenous lipids are soy based (Intralipid®) and contain significant amounts of both phytosterols and long chain polyunsaturated fatty acids (LCPUFAs) resulting in hepatic inflammation [111]. LCPUFAs include both proinflammatory omega-6 and anti-inflammatory omega-3 fatty acids - both of which compete for enzymes [112][113][114]. Decosohexanoic acid and eicosapentaenoic acid are omega-3 fatty acids that interfere with the arachidonic acid inflammatory pathway and downregulate associated inflammatory eicosanoids[115]. Therefore, it appears that the ratio of omega-6 to omega-3 fatty acids may be important. Soy based lipid emulsions have a ratio of approximately 5.5:1, whereas the optimal ratio to minimize inflammation is thought to be between 1:1 and 4:1 [116].

The intravenous administration of standard soy based fat emulsions at greater than 1 g/kg/day is associated with the evolution of hyperbilirubinemia in adults. Conversely, there are data to suggest that the infusion of omega-6 lipid emulsions at 1 g/kg/day or less helps to prevent and treat biochemical evidence of intestinal failure associated liver disease (IFALD) in children [117]. Studies have more recently shown that the provision of lipids in the form of parenteral fish oil emulsions (omega-3 fatty acids) at 1 g/kg/day normalize hyperbilirubinemia in the large majority of patients with IFALD[118][119]. Importantly the use of these omega-3 formulations at 1 gram/kg/day appears not to be associated with evidence of biochemical fatty acid deficiency [120]. At the same time, many providers have used a lipid minimization strategy where soy based emulsion is given at lower doses (1 g/kg/day compared to 2 to 3 g/kg/day) with promising results in children [121]. It should be noted that it is difficult to separate the effect of lipid minimization from the specific type of lipid used since there are no studies comparing the effectiveness of the lipid restriction now used with both fish oil and soy based formulas. At present, omega-3 formulas are not FDA-approved and may be used only by directly obtaining compassionate use permission.

Despite some promising results in preventing IFALD, there are still some children who continue to have progressive cholestasis and eventual cirrhosis necessitating transplant. Another alternative intravenous lipid that is being used selectively is SMOF lipid. This is an emulsion composed of 30% soybean oil, 30% medium chain triglycerides, 25% olive oil and 15% fish oil. SMOF has an omega-6 to omega-3 fatty acid ratio of about 2.5:1 [122]. Initial results in neonates suggest an improvement in hyperbilirubinemia when comparing SMOF to Intralipid [122]. Other groups have combined fish oil with soy oil and/or olive oil achieving similar improvement in hyperbilirubinemia in small series [119][123].

There is considerable optimism that the incidence of IFALD is decreasing significantly in pediatric patients with the advent of novel lipid intervention strategies. However, randomized prospective trials need to be completed to more fully explore the type and dose of lipid emulsion necessary to provide hepatoprotection while optimizing growth and development.

What is refeeding syndrome?

Refeeding syndrome (RFS) comprises the metabolic abnormalities and clinical symptoms that occur when malnourished patients are fed either enterally or parentally. The syndrome is generally characterized by low serum phosphate, magnesium, and potassium and reflects a change from catabolic to anabolic metabolism as cells start to take up these micronutrients[124]. Anyone with negligible food intake for greater than five days or with poor nutritional status is at risk for developing refeeding syndrome. A good predictor in pediatric patients is a body weight less than 80% of ideal [125]. If RFS develops and is not promptly treated, complications can include cardiac arrhythmia, hemolytic anemia, seizures, coma, and sudden death [126]. Hypophosphatemia can occur quickly (within 48 hours) and can lead to decreased survival because phosphate is a very important intracellular buffer and structural component of phospholipids and nucleic acids [124]. Hypomagnesemia and hypokalemia can lead to cardiac arrhythmias, seizures, abdominal pain, vertigo, and weakness. The most common approach to preventing and/or minimizing RFS is to either limit caloric intake or feed at full calories with aggressive correction of electrolytes. A randomized, controlled trial in critically-ill adults found that, although there was no difference in time spent in the intensive care unit or overall mortality, there were more infections in the group fed full calories compared to those who were calorie-restricted. All of the included patients had hypophosphatemia prior to the intervention [127]. However, in younger patients, who are acutely ill, but are otherwise at low risk for malnutrition, there appears to be little benefit to calorie restriction [128][129].

The best approach to prevent RFS is to identify patients at risk and then monitor nutritional intake, fluids, and electrolytes closely, ensuring the provision of at least 2 to 3 mmol/kg of intravenous potassium, 0.3 to 0.6 mmol/kg of intravenous phosphorous, and 0.2 mmol/kg of intravenous magnesium daily. When correcting RFS, thiamine and vitamins B12 and B6 should be repleted daily for ten days [124]. Current guidelines recommend slow, low energy refeeding with a gradual increase in energy intake. Although numerous refeeding guidelines exist, there are none specifically for children. It is also important to remember that RFS can occur in obese patients as well - especially after chronic weight loss from bariatric surgical procedures [130].

Outcomes

Neonates and children have markedly reduced protein and lipid stores when compared to adults [48]. Further metabolic stress in children exacerbates this lack of reserve by increasing net protein breakdown, the mobilization of free fatty acids, and gluconeogenesis [131]. Unfortunately, studies suggest that the daily caloric needs of critically-ill children are often not met. A multicenter, intensive care unit investigation showed that patients who received less than 66% of their estimated caloric needs during their intensive care unit stay had a significantly higher mortality[132].

Research and Future Directions

Are there nonessential amino acids which, when administered, may enhance outcome in critically-ill patients?

Multiple nonessential amino acids (those that may be ordinarily synthesized de novo within the human body) have been implicated as possibly improving outcome in critically ill patients. These include glutamine, arginine, proline, cysteine, and taurine. A postulated mechanism is that biosynthetic pathways become inadequate to meet demands imposed by critical illness, hence rendering these amino acids conditionally essential. Supplementation trials in adults have had conflicting results and no critically ill population group has been identified that has consistently benefited by the supplementation of selected nonessential amino acids [133][134][135]. Both the safety and efficacy of such interventions in children remains unknown.

How can the catabolic state be altered in the critically ill patient?

Stable isotope studies indicate that the catabolic state in critically ill and postoperative pediatric patients is characterized by increased protein breakdown and increased protein synthesis, with the former predominating, which overall results in net protein breakdown [131]. The catabolic state may be affected through nutritional intervention, such as dietary protein provision, by augmenting protein synthesis. Adequate anesthesia, analgesia, and underlying illness treatment may also limit protein degradation [136]. High dose insulin infusions and provision of dietary protein may significantly enhance protein synthesis in pediatric patients on extracorporeal life support, although this effect is quantitatively quite small [137]. The use of insulin to maintain tight glycemic control is not associated with a reduction in muscle protein breakdown in pediatric patients admitted to the intensive care unit following cardiopulmonary bypass[138]. Similarly the use of growth hormone, insulin-derived growth factor 1 (IGF-1), and testosterone have had variable success in altering the catabolic state and remain investigational [71].

What are the effects of lipid administration upon immune and liver function?

High doses intravenous lipid emulsions may result in hypertriglyceridemia, accumulation within the reticuloendothelial system (including the liver), decreased alveolar oxygen diffusion capacity, and increased infection risk [139]. Hence lipid administration in critically-ill children is generally limited to a maximum of 30 to 40% of total caloric intake in an effort to obviate immune dysfunction, although this practice has not been validated in formal clinical trials [71]. The provision of omega-3 fatty acids (“fish oils”) has an anti-inflammatory effect with decreased cytokine production in some models. The utility of omega-3 fatty acid administration and lipid restriction is being investigated in critically ill patients [140]. (see Complications)

What is the role of immunomodulating diets in the care of the critically ill pediatric patient?

Potentially promising but unproven immunomodulating nutrients in critical illness include arginine, glutamine, cysteine, nucleic acids, omega-3 fatty acids, selenium and vitamin E. Investigations pertaining to their use in critically ill patients are marred by the inclusion of heterogeneous clinical populations, methodologic errors, and the use of nutritional formulations that often contain multiple potentially active components. Studies and meta-analyses offer conflicting conclusions [133]. Large scale investigations in critically ill children are lacking.

Patient Care Guidelines

By what algorithm should enteral nutrition be initiated and advanced in the critically ill and postoperative pediatric patient?

Enteral nutrition is the safest and most economical means of providing calories and nutrients. Infectious complications are diminished by direct nutritional support of the intestinal mucosa [16]. Pediatric formulas can be given orally or by enteral feeding tube. A gastrostomy should be considered when oral feeding is not possible or safe for a prolonged period of time.

See Enteral Nutrition

enteral nutrition algorithm

By what algorithm should parenteral nutrition be initiated and advanced in the critically ill and postoperative pediatric patient? Parenteral nutrition is a lifesaving modality for patients who are unable to take adequate enteral nutrition [69]. Premature infants require slow progression of feeding to allow tolerance and prevent necrotizing enterocolitis. Early initiation of parenteral nutrition is indicated for sick or premature infants because of the additional requirements for development and growth. Older children and adults may develop significant morbidity if starvation exceeds five to seven days, especially patients with head injuries or burns who may be hypermetabolic. Other indications for parenteral nutrition include short bowel syndrome, radiation enteritis, intractable vomiting and diarrhea, severe acute pancreatitis and high output enterocutaneous fistulae.

see Parenteral Nutrition

parenteral nutrition algorithm

Perspectives and Commentary

To submit comments about this topic please contact the editors at NaT@eapsa.org.

Glossary

Basal Metabolic Rate (BMR): the amount of energy required by the body at rest and while fasted

Failure to thrive (FTT): Delayed growth with weight for age or weight for height below the 3rd percentile for age

Long-chain polyunsatureated fatty acids (LC-PUFA): long-chain fatty acids including decosahexaenoic acid (DHA) and arachidonic acid (AA), normally found in breast milk and felt to be important in human neurodevelopment.

Malnutrition: Inadequate or unbalanced intake of nutrients required to support normal growth and development

Respiratory Quotient: the ratio of carbon dioxide produced to oxygen consumed while nutrients are being metabolized

Resting Energy Expenditure (REE): the amount of energy required by the body for 24 hours during resting conditions (similar to BMR and often used interchangeably)

Total Energy Expenditure (TEE): The sum of BMR, specific dynamic action of food (energy produced as heat during food metabolism) and energy required for activity, losses and growth

Additional Resources

Links to anthropometric charts:

CDC and WHO growth charts: www.peditools.org

Newborn weight tool: www.newbornweight.org

CDC and WHO arm circumference and triceps skinfold: www.peditools.org

Links to nutritional screening tools:

Mini Nutritional Assessment: mna-elderly.com

Subjective Global Assessment: https://www.health.qld.gov.au…

Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP): stampscreeningtool.org

Discussion Questions and Cases

To submit interesting cases which display thoughtful patient management please contact the editors at NaT@eapsa.org.

An eleven year old boy with Crohn’s disease has a partial bowel obstruction due to terminal ileal disease. He has not been eating well for the past two months because of pain and intermittent emesis.

What is the best approach to determining whether or not this child is malnourished?

A newborn with a recently repaired congenital diaphragmatic hernia remains intubated in the intensive care unit. He has not been gaining sufficient weight despite providing what is felt to be sufficient calories.

How can his energy expenditure and caloric needs most accurately be determined?

An eight year old girl weighing 28 kg underwent a laparoscopic appendectomy five days ago. Although she initially tolerated some oral intake, she now has a significant ileus and is requiring nasogastric decompression.

When should parenteral nutrition be initiated and how should it be ordered with regard to calories, fluids, macro- and micronutrients?

Additonal questions are in SCORE Nutrition conference prep

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Last updated: May 30, 2017

Citation

TY - ELEC T1 - Nutrition ID - 829018 A1 - Kenney,Brian,MD, MPH AU - Piper,Hannah, AU - Relles,Daniel, AU - Jaksic,Tom,MD, PhD Y1 - 2017/05/30/ PB - Pediatric Surgery NaT UR - https://www.unboundmedicine.com/medline/view/Pediatric-Surgery-NaT/829018/all/Nutrition ER -