Chapter 60: Nutritional Support and Electrolyte Management

Dietary choices impact disease. In the outpatient setting, dietary choices influence our risk for heart disease, cancers, obesity, diabetes, and stroke^1,2; poor dietary choices increase the chance for developing these chronic and acute conditions, many of which are among the leading causes of morbidity and mortality in the United States and the world.^3,4 Five of the 10 leading causes of death in the United States are directly associated with dietary factors (heart disease, cancer, stroke, diabetes, and atherosclerosis).⁵ And dietary interventions can be a primary treatment for these conditions, with outcomes equivalent to or better than drug therapy.⁶

In the inpatient, hospital-based setting, a patient’s nutritional status also impacts clinical outcomes. This notion was first reported in surgical patients in the year 1936, in a study demonstrating that patients with baseline malnutrition undergoing peptic ulcer surgery had mortality rates of 33% compared to 3.5% in well-nourished controls.⁷ This pattern has been reported repeatedly since then, with preoperative malnutrition leading to increased morbidity and mortality in the surgical and trauma literature. With the prevalence of baseline malnutrition among hospitalized medical and surgical patients as high as 40%,^8,9 many patients are at high-risk for poor outcomes and complications.

Anticipating and addressing a hospitalized patient’s dietary needs can therefore substantially impact their disease as well as their outcome. Simply put, providing adequate nutrition is essential to high-quality patient care. Given the extreme physiologic, metabolic, and homeostatic changes that can occur after severe injury, nowhere in medicine is this more true than in trauma, surgery, and critical care.

This chapter is about nutrition, the inflammatory stress responses to injury, and the nutritional needs of the polytrauma patient, for both macro- and micronutrients. The first major section “Nutritional Support” provides a thorough, up-to-date guide on nutrition: first, nutritional needs and requirements are addressed, in both the healthy patient as well as the critically ill, hypermetabolic trauma patient; second, we will outline the specifics of nutritional intervention, including both enteral and parenteral nutritional support; lastly, we cover some special patient populations. The second major section of this chapter, “Electrolyte Management,” is divided into the management strategies of four major electrolytes and their associated abnormalities—sodium and disorders of water balance, potassium, phosphorus, and magnesium.

Nutritional Needs

Ensuring a patient meets their nutritional needs is vitally important: it is as fundamental to good outcomes as attending to their cardiac function, respiratory status, venous thromboembolism risk, and infection concerns. Addressing the energy and nutrient requirements in the multiple-injured trauma patient requires knowing the needs of a patient in good health as well as knowing how the post-injury inflammatory stress response can impact those needs.

This section is divided into two parts. The first part discusses nutrient utilization and requirements in a state of normal health (and thus trauma patients with only minor injuries), including a thorough investigation of all macronutrients and micronutrients. The second part reviews nutrition in abnormal states of health, particularly in the most severely injured trauma patients, and how their hypermetabolic, hypercatabolic, hyperdynamic inflammatory stress response impacts nutritional needs.

Normal Nutritional States of Health

Normal health implies homeostasis, when there is balance among the metabolic regulatory mechanisms that act to keep the body in a smooth, continuous condition of regular physiologic function. Part of homeostasis involves ensuring that the body has adequate energy reserves as well as other nutrients to maintain this physiologic normalcy.¹⁰ In this section we discuss nutrient utilization and requirements in a state of normal health, and provide a conceptual framework underlying the basis and terminology of nutritional needs support. We will cover the three principle classes of food—namely proteins, carbohydrates, and fats (collectively the macronutrients)—as well as the other fundamental compounds without which humans could not survive: water and the micronutrients (vitamins and minerals). See Box 60-1.

Nutrient Utilization and Needs

Humans need energy to live: to do physical work; to maintain body temperature and concentration gradients; to transport, synthesize, degrade, and replace molecules which make up our body’s tissues.¹¹ This energy is generated by the oxidation of various organic substances consumed in the diet, primarily the macronutrients: carbohydrates, fats, and proteins. The energy produced in the human body by the oxidation of macronutrients is the same as the heat of combustion of these substances in a lab. The major difference is that the body’s oxidation is carried out through multiple steps, allowing humans to capture the energy in an intermediate chemical form.

A human’s daily energy requirement allows for maintenance of metabolism and activity. This requirement is the level of energy intake from food that will balance energy expenditures. While the word “energy” is often used repeatedly in a discussion of nutrition, its use in this sense is overly general and nonspecific. “Energy” can refer to food energy, basal energy expenditure, potential energy, energy density, or many other aspects of nutrition. As it relates to what we eat, food energy (as measured in kilocalories or kilojoules) specifically refers the energy derived from protein, carbohydrates (aka sugars), and fat.

In addition to energy requirements, humans also have nutrient requirements, and therefore need protein (for essential amino acids), fats (for essential fatty acids), water, vitamins, and minerals to survive. Macronutrients and micronutrients, along with water, build the basis of nutrient utilization and needs. Each will be reviewed here:

• Energy = Calories = kilocalories

  A patient’s daily kilocaloric needs (aka total energy requirement) are often referred to as their total energy expenditure (TEE); strictly speaking, this is not completely accurate, as the energy needs (aka requirements) are determined by the energy expenditure. A better way to think about this is to appreciate that energy requirements are based on estimates of energy expenditure.¹⁰

  The basal metabolic rate (BMR) reflects the energy needed to sustain and maintain metabolism; it is the energy cost of living. The BMR describes “the rate of energy expenditure that occurs in the postabsorptive state, defined as the particular condition that prevails after an overnight fast, that subject having not consumed food for 12–14 hours and resting comfortably, supine, awake, and motionless in a thermoneutral environment. This standardized metabolic state corresponds to the situation in which food and physical activity have minimal influence on metabolism.”¹¹ Basal energy expenditure (BEE), expressed as kcal/24 h, is the BMR extrapolated to 24 hours.

  Total energy expenditure (TEE) in healthy subjects is made up of three components: REE (and thus BEE), AEE, and DEE.¹¹

  1. Resting energy expenditure (REE), or energy expenditure under resting conditions; REE is about 60% of TEE. Note that REE is made up of three variables: Basal energy expenditure (BEE), thermoregulation, and energy expended in depositing new tissue. As such, REE is usually about 10–20% higher than BEE. REE therefore includes all the homeostatic reactions in the human body.

  2. Activity induced energy expenditure (AEE), which is about 30% of TEE. AEE is highly variable, depending on baseline physical activity level as well as a person’s physical capacity. For example, in obese patients, with a decreased level of activity, an AEE estimate of 30% TEE is accepted to be too high. However, in very active individuals, AEE can be over 50% of TEE.¹¹

  3. Diet-induced energy expenditure (DEE), which is about 10% of TEE. This is also referred to as the thermic effect of food (TEF).

  From these three components, we see that four factors determine an individual’s daily energy requirements: gender, age, body size, and level of activity. Males require more kilocalories than females; the young require more kilocalories than the old; large people with more body mass require more kilocalories than smaller individuals; and the more active you are the higher your kilocaloric needs.

  For example, a nonactive, frail 85-year-old lady who weighs less than 100 lb and is 4 ft tall requires only 1000 kcal/d, while a college-age male athlete weighing 220 lb and standing over 6 ft tall needs over 3000 kcal/d. On average, most adult men need about 2500 kcal/d and most adult women need about 2000 kcal/d.

  Estimated energy requirements (EER) should, as far as possible, be based on estimates of energy expenditure. Energy expenditure can be derived in two ways: direct measurement or predictive equations (mathematical formulas).

  The first method to determine EER is by direct measurement of TEE. This can be done by whole body calorimetry (the gold standard), indirect calorimetry, or the doubly labeled water (DLW) technique. These methods are rarely used nowadays and are not discussed in this chapter; a thorough discussion can be found elsewhere.^11,12

  The second method to determine EER is by predictive equations that estimate TEE. Three common formulas are: a simplified approach using ideal body weight, a more complex and traditional approach using the Harris-Benedict equation (rarely used clinically anymore but presented for its historical significance), and a more modern predictive equation developed by the Institute of Medicine (IOM). Other excellent predictive equations not presented here include the Mifflin-St Jeor equation¹³ and the Penn State equations.^14,15

• Ideal body weight TEE equation

  The easiest formula to use to calculate energy requirements is based on a predictive equation for TEE using a patient’s ideal body weight (IBW):

  

  This will give you a person’s kilocalorie energy needs over 24 hours. To find a person’s IBW, IBW tables exist as do user-friendly smartphone applications. This simple formula is useful for clinical purposes as an initial estimate. Given the components of TEE, however, the fixed value of 30 kcal/kg will vary depending on the clinical circumstances, such as during the post-injury stress response or after a major burn.

  It is important to know that IBW, much like daily caloric needs, is derived from a calculation. There are various methods to calculating IBW; a few of the more well-known methods to calculate IBW were derived by Lorentz in 1929,¹⁶ Robinson in 1983,¹⁷ Devine in 1974,¹⁸ and Hamwi in 1964.¹⁹ They all produce approximately the same value of IBW,²⁰ and are all derived by calculations based on height and gender. IBW should not be confused with two other types of body weight calculations, namely the adjusted body weight (ABW)²¹ and the lean body weight (LBW).²²

  While IBW is recommended in this simplified predictive formula for calculating kilocaloric needs, there are exceptions. In obese patients, IBW is much lower than their actual body weight. If a patient is overweight to the point that actual body weight is greater than 30% over calculated IBW, the adjusted body weight (ABW) is recommended for determining daily caloric needs (ABW can also be found in tables, smartphone/tablet applications, or online calculators).

  LBW, meaning the total weight of all tissue in the body excluding fat (sometimes also referred to as fat-free mass, FFM), is the weight measure most closely correlated to BEE, REE, and TEE.¹¹ LBW explains about 70–80% of the variance in energy expenditure. The other 20–30% is affected by age, gender, baseline nutritional state, inherited variations, and different endocrine states.

  LBW is extremely variable at different stages of life. For example, from birth to adulthood: the brain increases its LBW fivefold; the liver, heart, and kidneys, which are even more metabolically active, increase 10- to 12-fold; muscle multiplies its LBW by about 40-fold.²³ The lean tissue content of the body declines with age, and this accounts in part for a progressive fall in basal metabolic rate in relation to body size.²⁴ In the elderly there is a decrease in the proportion of skeletal mass, as well as muscle.²⁵ For all of these reasons, IBW is used to predict energy expenditure, not LBW.

  There are times when it is important to calculate a healthy patient’s basal energy requirements (BEE). To do this via the IBW method, a patient’s BEE would be

  BEE = IBW (in kg) × 24 kcal/kg

  BEE is thus IBW multiplied by a smaller factor of 23–24 kcal/kg. TEE equation of 30 kcal/kg represents a 25% increase over BEE of 24 kcal/kg.^26,27 Very limited activity increases the requirement to 28 kcal/kg.

• Harris-Benedict equation for BEE

  The Harris-Benedict equation (HBE)²⁸ is perhaps the best known equation to determine a patient’s total kilocaloric needs over a 24-hour period. The equations were derived using indirect calorimetry. There are separate equations for males and females, and each is based on weight (in kilograms), height (in centimeters), and age (in years). The HBE equations predict BEE (not TEE):

  
  

  Once the BEE has been calculated from the HBE, one needs to apply an activity factor multiplier to determine the TEE; the predicted value for TEE is then used as the EER for 24-hour kilocalorie needs. To do this, the baseline HBE values are multiplied as follows; the multipliers are the same for males and females²⁹:

  

• Institute of Medicine TEE equations

  The Institute of Medicine (IOM) has published a set formula that predicts TEE based on age, height, weight, and physical activity level (PAL). They were derived using the DLW method for directly measuring TEE, and represent a more modern approach to determining estimated energy requirements (EER)¹¹ (the IOM equations were defined in the year 2005 while the HBE was derived nearly 100 years ago, in the year 1918).²⁸ These IOM TEE equations have replaced the Schofield Equation³⁰ to define and develop the FDA’s dietary guidelines and formulate RDAs.

  The IOM TEE prediction formula to calculate EER for males ages 19 years and older is (with age in years, weight in kilograms, and height in meters):

  

  where PA is the physical activity coefficient:

  • PA = 1.00 if sedentary

  • PA = 1.11 if low active

  • PA = 1.25 if active

  • PA = 1.48 if very active

  The IOM TEE prediction formula to calculate EER for females ages 19 years and older is (with age in years, weight in kilograms, and height in meters):

  

  where PA is the physical activity coefficient:

  • PA = 1.00 if sedentary

  • PA = 1.12 if low active

  • PA = 1.27 if active

  • PA = 1.45 if very active

  It has been suggested that the HBE and IOM equations for TEE do not add that much more accuracy beyond the simple IBW equations; this is confirmed in multiple guidelines which base TEE recommendations on predictive formulas.^31,34 Please see Table 60-1 to get a sense for how these equations produce different EER estimates.

• Protein

  Proteins are large, nitrogenous organic compounds that are made up of long chains of amino acids; there are 20 different amino acids in our body’s proteins. Proteins exist in every cell, tissue, and organ in the human body, and are an essential part of all living organisms. Proteins are major structural components of muscle, bones, skin, and collagen; along with amino acids, proteins function as enzymes, antibodies, membrane receptors, hormones, and carriers of nutrients in the blood. Protein balance is often referred to as nitrogen balance.

  Humans obtain proteins solely from the diet; once ingested, proteins are digested into their component amino acids. Dietary proteins come in two general forms: complete proteins and incomplete proteins. Complete proteins (aka whole protein; high-quality protein) come from animal-based products and supply all the amino acids, most importantly a group called the essential amino acids. There are nine essential amino acids (aka indispensable amino acids) which cannot be synthesized de novo by humans: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Incomplete proteins come from plants and lack one or more of the nine essential amino acids. When two or more incomplete proteins are combined to provide adequate amounts of all nine essential amino acids, they are referred to as complementary proteins.

  Unlike fat (stored as adipose tissue) and carbohydrates (stored as glycogen in the liver and skeletal muscle), protein is not stored in the body. In contrast to other sources of energy, if more protein is ingested than is needed for metabolic purposes, all that excess nitrogen is metabolized and the end products are excreted. If less protein is ingested than is needed for homeostasis, leading to a persistent negative nitrogen balance, the body adapts by breaking down muscle, leading to a loss of LBW.¹⁰ See Box 60-2.

  What is a safe level of intake of dietary protein per 24 hours, and how are the nutritional protein needs determined? The protein requirement of an individual is defined as the lowest level of dietary protein intake that will balance the losses of nitrogen from the body (principally in the urine, but also in feces and through the skin) in persons maintaining energy balance at modest levels of physical activity.²³ Furthermore, we cannot simply maintain nitrogen balance; rather we must ensure that the required dietary protein intake includes both the essential amino acids and the nonessential amino acids. The amount of essential amino acids required in a healthy adult diet is 27.7%.³⁵

  There are two general methods for determining the daily recommended allowance for protein: direct measurement or predictive mathematical formula. The first method is to measure nitrogen loss, when the diet contains no protein, which will provide an estimate of nitrogen requirement. This has been done in nitrogen balance studies by collection of nitrogen losses in the urine, feces, skin, and sweat/secretions and subtracting these losses from measured nitrogen content of protein intake; the process is repeated multiple times, across several levels of protein intake, over many days, each time ensuring metabolic steady state has been reached. This process is quite impractical, though it is this process which forms the basis for estimating protein requirements using the predictive formula methodologies.¹⁰

  The second method is by one of two different mathematical formulas: the first based on a person’s weight, the second based on daily energy requirements.

  • Protein requirement using weight-based method

    Determining dietary protein needs for healthy subjects using IBW is based on long-term nitrogen balance studies.³⁵ Specific equations have been derived from these studies, by both the World Health Organization³⁶ as well as the Institute of Medicine,³⁷ which provide nearly identical results. The Recommended Dietary Allowance (RDA) equation is ^36,37,38:

    

    There are three factors that went into determining this 24 hour requirement value. The first is the average amount of high-quality protein needed to maintain nitrogen balance: 0.6 g protein/kg IBW/d. The second is a safety factor to ascertain that 95% of the healthy population’s protein needs are covered: 0.15 g protein/kg IBW/d. The third is a buffer to allow for intake of proteins which are not high-quality proteins: 0.05 g protein/kg IBW/d.³⁵

    The equation is the same for both healthy adult men and women. While differences in lean body weight (LBW) exist between genders, as well as older and younger, these differences are offset partially by differences in weight.³⁷ Accordingly, there is simply one equation for all healthy adults.

  • Protein requirement based on energy need

    The most recent dietary reference intakes (DRIs)^11,37 for macronutrients are designed to reflect a broadened view of protein needs, in relation to carbohydrate and fat requirements. This method, termed “acceptable macronutrient distribution range” (AMDR), more clearly reflects the interrelation between the macronutrients and allows for some level of flexibility in diet planning. If an individual consumes below or above the AMDR range, there is potential to affect long-term health by increasing the risk of chronic diseases, as well as increasing the risk of insufficient intakes of essential nutrients.³⁹ See Table 60-2 for AMDRs for all macronutrients.

    The AMDR for dietary protein is a safe range of intake, from 10 to 35% of the total daily kilocalorie requirement.³⁷ This affords the ability to provide protein intake in excess of the RDA but within the AMDR; this has spawned the term “flexible calories,” because a clinician can use the AMDR for all three macronutrients to create varied dietary plans while still achieving kilocalorie needs.³⁸

    This alternative to the weight-based approach to determining protein needs is therefore based on the calculation for daily energy requirements. For example, the AMDR for protein is 10–35%; the FDA bases the daily recommended value (DRV) for protein on all food labels in the United States on a 10% rule (the low end of the AMDR for protein): 10% of 24-hour energy needs (as measured in kilocalories) should come from protein.⁴⁰ The equation for the 10% rule is

    

    A simpler way to calculate this is

    

    While the FDA uses 10%, which is at the RDA level of 0.8 g protein/kg/d, one needs to consider the patient circumstances, and thus consider other values within the AMDR for protein. For example, there is good data to show that physically active people should have protein intakes in the range of 1.2–2.0 g protein/kg/d (15–25% of energy from protein).^41,42,43 There is other research which now demonstrates the benefits of increased protein intake in elderly adults to levels nearly double the RDA of 0.8 g protein/kg/d, the goal being to preserve lean body mass and promote functional ability with age.^44,45,46

• Carbohydrates

  Carbohydrates are organic compounds which contain only carbon, hydrogen, and oxygen atoms in a ratio usually of 1:2:1; most carbohydrates, but not all, follow the general chemical formula is C_n(H₂O)_n. What distinguishes one carbohydrate from another is the different ways the atoms combine.

  Carbohydrates (aka carbs) are the most important energy source for humans, particularly the brain, which is a carbohydrate-dependent organ. In this manner, carbs can be thought of as the storage and transportation form of energy. Carbohydrates, however, are more than simply energy. Carbs also play major roles in our immune system, reproductive system, blood clotting, and cell structure; DNA and RNA are carbohydrate-based chains of molecules. The chemistry behind the structure of sugars is extremely complicated, and some have maintained that the genome is simple compared to the “glycome.” The study of the glycome is referred to as “glycomics,” and the science of carbohydrates’ role in life is termed “glycobiology.”

  Carbohydrates are often referred to as sugars, or saccharides. Naturally occurring saccharides are produced by photosynthetic plants. Unnatural sugars (aka processed sugars; refined sugars; artificial sweeteners) are simply chemical compounds made in a lab, and lack vitamins and minerals; they are referred to an “empty calories.” The body digests most carbohydrates in the diet into glucose (C₆H₁₂O₆; aka blood sugar). Glucose is then used in two ways: either as a source of energy via cellular respiration or stored as glycogen in the liver, skeletal muscle, and other tissues (excess glucose can also be stored as fat).

  A monosaccharide is a carbohydrate in its elemental form, with one sugar unit. When two monosaccharides, or sugar units, combine they form a disaccharide. When three to ten monosaccharides join they form an oligosaccharides, which have complex, varied, and critical biological functions. Polysaccharides are built from any combination of monosaccharides and disaccharides; examples of polysaccharides are glycogen, the storage form of glucose, and starch.

  Carbs come in two types: simple or complex, the difference being their underlying chemical structure. Simple carbohydrates are sugars in their simplest form, either one (monosaccharides) or two (disaccharides) sugars. Examples of monosaccharides include glucose, fructose (aka fruit sugar), and galactose; examples of disaccharides include sucrose (aka table sugar) and lactose (aka milk sugar).

  Complex carbohydrates are made up of three or more simple carbohydrates bonded together into one larger compound; polysaccharides and oligosaccharides are complex carbs. Complex carbs come in two dietary forms: starch and dietary fiber. Starches are digested into sugars for energy; in addition to providing kilocalories, starches also contain vitamins and minerals. Complex carb-containing foods are popularly referred to as “starchy” foods.

  Dietary fibers (aka roughage; bulk; nondigestible carbohydrates) are plant-derived complex carbs that the human body cannot digest or absorb, meaning fiber traverses the GI tract without being broken down. The health benefits of fibers are numerous, and include helping to control weight by causing satiety, aiding digestion, preventing constipation, attenuating blood glucose levels, and decreasing serum cholesterol.³⁷ There are two general types of fiber: soluble and insoluble. Soluble fiber dissolves in water, and forms a gel-like substance in the GI tract that helps to lower blood cholesterol and glucose levels. Insoluble fiber doesn’t dissolve in water, and therefore promotes movement of material through the GI tract and helps with constipation and laxation.

  What is an average requirement for carbohydrates per 24 hours, and how are the nutritional needs for carbohydrates determined? In general, carbohydrate needs are determined as a percentage of 24-hour energy requirements.^11,37

  • Carbohydrate requirement based on energy needs:

    The RDA for carbohydrates is based on a minimum amount necessary to cover the glucose needs of the carbohydrate-dependent central nervous system.¹¹ With this in mind, when the FDA set the DRV for carbohydrates on all food labels in the United States, they used a very conservative value of 60%: 60% of 24-hour kilocalorie energy needs should come from carbohydrates.⁴⁰

    A more modern approach to determining daily carbohydrate needs is to consider the Institute of Medicine’s Acceptable Macronutrient Distribution Range (AMDR) for carbohydrates.¹¹ The AMDRs delineate upper and lower bounds for the percentage of daily calories provided from all macronutrients; these safe ranges recognize the interrelation between the macronutrients, and allow flexibility in creating customized diets to individual patient needs.

    For carbohydrates, the AMDR is from 45 to 65% of total daily kilocalorie requirement (see Table 60-2).³⁷ This means that carbohydrate-derived energy can safely make up anywhere from 45 to 65% of total energy needs. The calculation for determining 24-hour carbohydrate requirements is based on 4 kcal of energy being produced from every gram of carbohydrate consumed (note that for parenteral nutrition calculations the conversion is 3.4 kcal/g). For example, using the FDA’s DRV of 60%, the equation is

    

    To determine other values, one simply substitutes for any percentage, from 45 (use 0.45 in the equation) to 65% (use 0.65 in the equation).

• Fat

  Fats are an essential nutrient, and a key part of our diet. They are characterized by being insoluble in water, nonvolatile, and greasy to touch. Fats are sometimes referred to as lipids, though technically speaking fats are a member of the lipid family.

  Lipids are a group of naturally occurring molecules that are derived from one of two common biochemical subunits (ketoacyl or isoprene). Lipid compounds include fatty acids (from which fats are derived); glycerolipids (triglycerides; diglycerides; monoglycerides; collectively aka glycerides); glycerophospholipids (aka phospholipids); sterol lipids (such as cholesterol and steroids); saccharolipids (such as lipopolysaccharides in gram negative bacteria); and others (see Ref. 11 for more details).

  Fats provide a needed source of energy for the human body. As an energy source, fat produces 9 kcal energy per gram, which is over twice as many kcal as can be derived from carbohydrates (4 kcal/g enterally; 3.4 kcal/g parenterally) and protein (4 kcal/g). For this reason fat is referred to nature’s storehouse of energy. Fats are necessary for the body to absorb the fat-soluble vitamins A, D, E, and K. Fats help insulate the body, and keep skin and hair healthy.

  Fats also provide humans with the essential fatty acids: linoleic acid and linolenic acid (note that linoleic acid is the precursor to arachidonic acid, so technically speaking arachidonic acid is not considered essential). Humans can synthesize all but these two essential fatty acids. Fats can be synthesized from the breakdown products of proteins, carbohydrates, or other fats (using acetate as an intermediate metabolite).

  The essential fatty acids are crucial for membrane structure lipids, cell-signaling pathways, brain development, controlling inflammation, and blood clotting. Prostaglandins are hormone-like compounds derived from arachidonic acid, and are involved in many vital functions in the human body.

  As a chemical compound, fats contain carbon, hydrogen, and oxygen with the defining feature that they are arranged as a hydrocarbon chain skeleton, with a carboxyl group (-COOH) at one end and a methyl group (CH₃-) at the other. Fats are made from various fatty acids, which contribute approximately 95% of the total weight to various fats; the other 5% is from a backbone molecule to which the fatty acids bond, glycerol (and other occasionally attached molecules). Fatty acids are differentiated by the number of carbon atoms in their carbon skeleton as well as the number of carbon to carbon (C=C) double bonds. These differences lead to variations in structure and function. There are more than 100 different fatty acids in the human body, though less than 20 contribute to the majority of fats.

  Fats are classified as either unsaturated or saturated. Unsaturated fats have at least one C=C double bond in the carbon skeleton, which gives them a low melting temperature. They are often liquids at room temperature, known as oils. There are two types of unsaturated fats: monounsaturated and polyunsaturated. Monounsaturated fats have only one C=C double bond in the carbon skeleton. Polyunsaturated fats have two or more C=C double bonds in the carbon skeleton. Polyunsaturated fats include the two essential fatty acids: omega-3 polyunsaturated fats (linolenic fatty acid) and omega-6 polyunsaturated fats (linoleic fatty acid).

  Synthetic fats are unnatural, unsaturated fats created in an industrial lab when hydrogen is added to liquid vegetable oil (a natural unsaturated fat) to create solid fat. These fats are used mainly as preservatives for food and to add texture. Synthetic fats come in two types: hydrogenated fats and partially hydrogenated fats (aka trans fats; trans fatty acids). Trans fats have been proven to increase cholesterol and the risk for heart disease,^47,48 and have a detrimental effect on the brain and nervous system⁴⁹; in short, they have no benefit to human health.¹¹ It should be noted that there are some trans fats that are naturally occurring, found in animal fats.

  Saturated fats are so named because the carbon skeleton in these fats is saturated with hydrogen bonds, and therefore have no C=C double bonds. These fats are solids at room temperature, indicating a high melting temperature. They are generally referred to as the solid fats and come from two general sources: the primary source is animals, including meats and dairy products (all animal-based saturated fats also contain cholesterol). The second source is certain plants. Saturated fats were once thought to be linked to coronary heart disease and increased cholesterol levels, though that is being questioned by more recent data.⁵⁰

  Cholesterol is an organic sterol lipid molecule, synthesized by all animal cells. Cholesterol is an essential component of animal cell membranes, and is the precursor to steroid hormones, bile salt (it was first discovered in gallstones), and vitamin D. It is found in all foods containing animal fat; cholesterol is not found in significant amounts in plant sources.

  Triglycerides are lipid compounds derived when one molecule of glycerol combines with three fatty acids. Triglycerides are the major storage form of fat in human adipose tissue; the hydrolysis of triglyceride ester bonds is the first step in fat metabolism.

  What is an average requirement for fat per 24 hours, and how are nutritional fat needs determined? Neither an adequate intake (AI) level nor a Recommended Daily Allowance (RDA) exists for total fat. This is because there is not sufficient data to determine a level below which intake is inadequate or above which chronic diseases are prevented.¹¹ The acceptable macronutrient distribution range (AMDR) for fat for healthy adults is 20–35% of the total daily kilocalorie requirement.³⁷ Accordingly fat needs are determined as a percentage of 24-hour energy requirements.

  • Fat requirement based on energy needs

    The AMDR for fat is 20–35% (see Table 60-2). This range was set to ensure that the essential fatty acids were consumed in adequate amounts. The FDA has based its DRV for fat on a value of 30%: 30% of the 24-hour energy needs (as measured in kilocalories) should come from fat.⁴⁰ The equation to calculate 24-hour fat requirements is (using 30%, which can change depending on the percentage desired):

    

    To ensure intake of adequate dietary amounts of the essential fatty acids, approximately 10% of total daily kilocalorie intake should come from longer-chain polyunsaturated fats (see Table 60-2)³⁷:

    • Omega-3 polyunsaturated fat (linolenic fatty acid) intake should be in the range of 0.6–1.2% of 24-hour kilocalorie needs

    • Omega-6 polyunsaturated fats (linoleic fatty acid) should be in the range of 5–10% of 24-hour kilocalorie needs

    Current, dietary recommendations also maintain that humans should consume less than 10% of total energy from saturated fats.

• Water

  The human body is made up of 60% water, and on average, 60% of an adult’s total body weight is water.⁵¹ Water is the basis of all fluids in our body: for example, bile is 90% water; blood is 92% water; cerebrospinal fluid is 99% water. Water is also the basis of all organs and tissues in our body: bone is 31% water; the brain and heart are 73% water; muscles and kidneys are 79% water; and lungs are 83% water.⁵² Total body water (TBW) is distributed between the intracellular fluid (ICF; 65% TBW) and extracellular fluid (ECF; 35% TBW); of the TBW in the ECF, 79% is in the interstitial space and 21% is intravascular in plasma.

  Water is made up of three atoms: two hydrogen and one oxygen. The simplicity of the water compound belies its importance, its versatility, and its complexity, both in terms of its physical and chemical properties. Water is the solvent, the medium, and the participant in most biochemical and physiological reactions occurring in our bodies; it absorbs and releases metabolic heat; it is attracted to itself and many other substances, and has tremendous surface tension and strength.

  Human life and cellular homeostasis depend on water: we could live roughly a month without macronutrients; we can live only a few days without water. Once reaching 10–14% dehydration, risk of death increases rapidly, approaching irreversibility.⁵¹ It is via water that carbohydrates and proteins are metabolized; aqueous solutions are the universal transporter of macronutrients, oxygen, and waste; cellular hydration is a crucial signal regulating cell metabolism and gene expression; water aids in digestion, is a lubricant for joints, and a shock absorber for the brain and spinal cord; water helps regulate body temperature through sweating and respiration.^51,52

  What is an average requirement for water per 24 hours, and how are the nutritional water needs determined? There is no RDA for water as there is not sufficient data to determine a level above which chronic diseases are prevented.⁵¹ The major risk associated with low intake of total water is dehydration, primarily in the acute setting, which can lead to metabolic and functional abnormalities. Accordingly, an Adequate Intake (AI) has been established for water below which intake is inadequate. These AIs were defined to cover minimal losses from temperate climates for a sedentary individual.

  The AI for total water per 24 hours to prevent dehydration in adult men is 3.7 L and in adult women is 2.7 L⁵¹; 80% of this is typically consumed by liquids, meaning healthy adult men should drink 3.0 L (13 cups) per day and women 2.2 L (9 cups); the remaining balance of water comes from food. This intake of water will replace respiratory, urinary, fecal, and insensible fluid losses. Higher intakes should be achieved in physically active people or those exposed to hot environments.

  Daily consumption of water below the AI may not translate into an added risk of dehydration because normal hydration can be achieved and maintained over a wide range of intake. Very importantly, the AI is therefore not a specific requirement.⁵¹ In healthy adults, fluid intake, driven by consumption of liquids and food at meals as well as by thirst, maintains total body water at normal levels, preventing dehydration. Body water balance is achieved when water gain and water loss are equal. Water gain occurs from consumption (sources of water include drinking water, water in beverages, and water that is part of food) and production (metabolic water). Water loss occurs from respiratory loss, urinary/renal loss, fecal/GI tract loss, skin loss, and insensible loss.

  The interrelationship between the macronutrients, other substances we consume, and water demonstrates the interconnectedness of homeostatic processes in humans. Increased or decreased intake of macronutrient as well as these other substances (such as caffeine, alcohol, and sodium) can and will affect water requirements.³⁹

  For example, for dietary proteins and amino acids, the major end product of their metabolism is urea. Urea requires water for excretion by the kidneys. Therefore increased protein intake requires increased water intake. For dietary carbohydrates, 100 g/d are required to prevent ketosis; consuming fewer carbs can increase ketone bodies, which require water to be excreted. Therefore increased ketosis requires increased water. And lastly, fecal water losses are increased with higher loads of dietary fiber; with increased fiber intake more water needs to be consumed to prevent dehydration.

• Micronutrients: vitamins and minerals

  The term “micronutrients” is used to refer to both vitamins and minerals. Vitamins are organic substances made by plants or animals; they are essential for growth and development. Vitamin deficiencies can be seen in the elderly (especially frail or institutionalized people with malnutrition), alcoholics (with associated malnutrition), illicit drug users, impoverished populations, and those in developing countries.

  There is a long list of vitamins that humans need; vitamins can be grouped together as follows:

  • Fat-soluble vitamins

    • vitamin A (retinol; including the carotenoids)

    • vitamin D

    • vitamin E

    • vitamin K

  • Water-soluble vitamins

    • B vitamins

      • biotin

      • folate (folic acid)

      • niacin (nicotinic acid)

      • pantothenic acid

      • riboflavin (vitamin B₂)

      • thiamin (vitamin B₁)

      • vitamin B₆ (pyridoxine)

      • vitamin B₁₂ (cobalamins)

    • vitamin C (ascorbic acid)

    • choline

  Please see Table 60-3 for vitamin functions, deficiencies, and toxicities; please see Table 60-4 for dietary reference intakes for the vitamins.^39,53

  Minerals, on the other hand, are inorganic elements that come from the earth, soil, and water; all minerals are found in the periodic table of elements.⁵⁴ Minerals are absorbed by pants from the ground, and humans consume minerals from eating these plants. Minerals are essential for human homeostasis, as the body uses them for normal bone, muscle, heart, and brain function as well as for making hormones.³⁹

  There is a long list of minerals that humans need. The minerals can be grouped together as follows:

  • Six macrominerals, which are needed in large amounts (in the range of grams per day); these are usually simply referred to as electrolytes (will be discussed in a later section):

    • Four cation electrolyte macrominerals:

      • Sodium (Na; element #11; an alkali metal)

      • Potassium (K; element #19; an alkaline earth metal)

      • Calcium (Ca; element #20; an alkaline earth metal)

      • Magnesium (Mg; element #12; an alkaline earth metal)

    • Two anion electrolyte macrominerals:

      • Chloride (Cl, chlorine; element #17; a nonmetal halogen gas)

      • Phosphorus (P; element #15; a nonmetal solid)

    • Nine trace minerals, which are needed in small amounts (in the milligram or less per day range):

      • Chromium (Cr; element #24; a transition metal)

      • Copper (Cu; element #29; a transition metal)

      • Fluoride (F, fluorine; element #9; a nonmetal halogen gas)

      • Iodine (I; element #53; a nonmetal halogen)

      • Iron (Fe; element #26; a transition metal)

      • Manganese (Mn; element #25; a transition metal)

      • Molybdenum (Mo; element #42; a transition metal)

      • Selenium (Se; element #34; a nonmetal solid)

      • Zinc (Zn; element #30; a transition metal)

    • Other minerals used by the body (not discussed in depth in this chapter; for more information see IOM report referenced here³⁹)

      • Sulfate (S, sulfur; element #16; a nonmetal solid)

      • Arsenic (As; element #33; a metalloid)

      • Boron (B; element #5; a metalloid)

      • Nickel (Ni; element #28; a transition metal)

      • Silicon (Si; element #14; a metalloid)

      • Vanadium (V; element #23; a transition metal)

    Please see Table 60-5 for trace mineral functions, deficiencies, and toxicities^39,55; please see Table 60-6 for DRIs for the trace minerals.^39,55

Abnormal Nutritional States of Health

Just as dietary factors contribute to increasing the risk for certain diseases, the reverse is also very true: disease processes can have a profound impact on nutritional status and needs. The optimal dietary requirements for a normal healthy adult (and thus the trauma patient with minor injuries), as discussed in the last section, may need to be adjusted for both acute and chronic conditions, in both the inpatient and outpatient setting, and for both medical and surgical disease.

This necessary alteration to nutritional needs occurs because in a state of abnormal health there can be a profound imbalance among the metabolic regulatory mechanisms which act to keep the body in a condition of normal physiologic function. The imbalance in metabolic and physiologic processes lead to changes in energy expenditures and thus energy requirements, driven by complex feedback mechanisms.¹¹ These changes to energy balance, triggered by metabolic and behavioral responses to disease, are crucial since bodily function depends on energy transformations. As such, changes to energy metabolism can profoundly alter baseline dietary requirements in an effort to return the body to normal function.

A body in homeostasis implies there is balance of physiologic function, and the body has adequate energy reserves and nutrients. Mild disturbances in homeostasis lead to adaptation, defined as a process by which a new or different steady state is reached, without loss of function.²³ An example is the increase in hemoglobin concentration that occurs when individuals live at high altitudes.¹¹ Another example, in response to a change or difference in the intake of food and nutrients, is the decrease in resting energy expenditure during starvation. Adaptation therefore involves changes in body composition that occur over a more extended period of time, without any discernible detriment to health.^11,23

More severe disturbances in homeostasis may be detrimental if they exceed adaptive capacity; these severe alterations to optimal function lead to accommodation. Accommodation involves relatively short-term adjustments, with the loss of less-vital physiologic function and attempts by the body to preserve and maintain the most essential functions, all in an effort to achieve homeostasis.¹⁰ Accommodation is therefore an adaptive response to a disturbance that allows survival but results in some degree of serious consequences to health or physiological function.^11,23 An example of accommodation, with a resultant initial breakdown in homeostatic mechanisms, is the hypermetabolic state which can be induced by major trauma and injury.

The Stress Response to Trauma and Injury

In addition to the anatomic injuries produced by a traumatic accident, injured patients are susceptible to developing a profound and systemic physiologic inflammatory response. This is known as the stress response to trauma, and can last for days to months after the initial injury. The stress response is multifaceted, driven by metabolic changes as well as alterations to the nervous, endocrine, and immune systems.^56,57 These changes can have severe negative downstream consequences, including inflammatory, immunologic, hematologic, and hemodynamic effects.^57,58 These changes can catalyze the systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), the post-injury multiple organ failure (MOF), and, at its worst, death.⁵⁹ The stress response can also affect protein, carbohydrate, and fat metabolism throughout the body,⁶⁰ which impacts the nutritional needs for both macronutrients and micronutrients.⁶¹

The metabolic response to trauma was first described in the early 1930s by a Scottish veterinarian-physiologist named Dr David Cuthbertson (he was later knighted for his work).^62,63 Cuthbertson showed increased protein metabolism after injury, and demonstrated that this was due to increased muscle catabolism. This hypercatabolic state was most pronounced from post-injury day 2–8, and in some patients lasted up to 2 months. The hypermetabolism was associated with corresponding physiologic changes to heart rate, body temperature, and oxygen consumption.^62,63

The systemic stress response to trauma is extremely complex, and driven by both the primary injury (tissue ischemia/reperfusion and tissue disruption) as well as secondary insults (blood transfusions, delayed operative procedures, infection), and is further compounded by innate gene expression and genetic polymorphisms.⁶⁴ Traditionally, the post-traumatic metabolic response is divided into two phases: an ebb phase and a flow phase, with the flow phase having both a catabolic period and an anabolic period.⁶⁵ These phases define the metabolic shifts after a major injury, define the deleterious systemic effects a local injury can produce, and define the alterations to energy requirements and nutritional needs after an injury.⁶⁵

• The ebb phase

  The ebb phase is the body’s short-term attempt to preserve energy after an injury. This period is marked by “depressed cellular metabolism” with decreased body temperature and oxygen consumption.⁶⁵ This stage is the period of traumatic shock, dominated by circulatory fluctuations that require resuscitation with fluids and blood products.^65,66 It represents the immediate consequences of the inciting injury, and can lead to whole body ischemia/reperfusion injury, and activation of a nervous system response with neuronal and humoral mediators.⁶⁴ The ebb phase of the stress response is also known as the nervous system phase; the ischemia/reperfusion phase; the immediate or first phase; and the resuscitation phase.^56,64

  As an example of the profound neuroendocrine changes during the ebb phase, alterations occur to thermoregulatory capacity of the hypothalamus, leading to a drop in core body temperature. The neuroendocrine-driven hypothermia from an overwhelming traumatic injury does not induce shivering, as would normally occur in environmentally driven hypothermia; it has therefore been compared to hibernation.⁵⁶ This is indicative of the protective hypometabolism of this resuscitation phase, as the body conserves energy to increase the chances of cellular survival.⁶⁷

  The ebb phase is typically measured in hours, usually from 8 to 24 hours.⁵⁸ The variable intensity and duration of the ebb phase are related to the severity of the injury⁶⁷: the more severe the injury, the shorter the ebb phase and the quicker the onset of the flow phase. Before returning to a normal metabolic state after an injury, the body must pass through the flow phase.

  The ebb phase can be so severe as to overwhelm the body’s adaptive mechanisms to a point beyond which the body cannot recover. This terminal ebb phase is simply referred to as irreversible shock. Physiologic mechanisms at work include profound hypothermia, depressed oxygen consumption below BEE, fall in cardiac output, vasoconstriction, increased blood viscosity, intravascular coagulation, and profound buildup of lactate due to anaerobic metabolism, failure of buffering capacity and concomitant acidosis, and eventual death.

  • Targeted metabolic therapy for the ebb phase

    Reducing initial damage caused by the early post-injury pathophysiologic processes in the ebb phase could determine a more favorable outcome,⁵⁶ especially for patients with evidence of post-injury early multiple organ failure (MOF).⁶⁸ The overall goal of targeted metabolic and nutritional therapy in this phase is to diminish the deleterious effects related to ischemia-reperfusion. Interestingly, the link between the hypermetabolic response and the post-injury MOF is evidenced by the fact that post-injury MOF was once referred to as the “hypermetabolism organ failure complex.”⁶⁹ Concepts such as damage control surgery⁷⁰ and damage control resuscitation⁷¹ have evolved as therapeutic stop-gaps to improve survival during this phase.

    While the one-hit model of MOF (example of “one-hits” are severe organ and soft tissue injury; hemorrhagic shock; profound hypoxia) stresses the importance of an overwhelming initial insult that precipitates severe SIRS and then MOF, there is also a two-hit model. In the two-hit hypothesis for the development of MOF, the first hits are less severe than in the one-hit model (example are milder hypotension, ischemia, and resuscitation), leading to a whole body proinflammatory reaction, but not SIRS. A second hit then occurs (sepsis, blood transfusion, second operation, mechanical ventilation), leading to SIRS and MOF.⁵⁹

    The first hits in both models occur during the ebb phase. Initial targeted treatment goals are to dampen the impact of the second hits.⁵⁷ For example, global hypoperfusion during the ebb phase can cause gastrointestinal (GI) tract hypoxia, which primes the intestinal microvasculature rendering it more susceptible to a secondary challenge.^56,72 Once that secondary challenge occurs in the form of reperfusion during resuscitation, the ischemic gut releases cytokines and proinflammatory mediators. This eventually leads to mobilization of neutrophils, and possible MOF,^59,73 as they cause direct tissue damage as well as systemic damage via release of cytokines.

    Theoretically, identification of patients at high risk for MOF could facilitate institution of early metabolic and/or nutritional therapies to dampen the proinflammatory response.⁵⁹ Supplementation with intraluminal glutamine has proved controversial⁶⁴ and pulse steroids⁷⁴ have been unsuccessful. Evidence of the benefits of early β-blockers⁶⁴ is mainly for burn patients.

• The catabolic flow phase

  What follows the ebb phase is the post-shock, post-resuscitation catabolic flow period, defined by systemic post-traumatic inflammation and increased metabolism as the body tries to repair itself.⁶⁶ These integrated metabolic, inflammatory changes occur in virtually all organs and tissues in the body.⁶⁰ The need for injury repair stimulates the hypercatabolic state, driven by cytokine mediators released from lymphocytes and macrophages, dominated by interleukin (IL)-6.^58,60 This leads to a functional redistribution of body cell mass to provide amino acids for gluconeogenesis and protein synthesis (see Fig. 60-1).^58,60,75 The catabolic state is maintained by proinflammatory cytokines and catabolic hormones for periods long after the acute trauma.⁷⁶

  The hypermetabolic changes are associated with neuroendocrine and immune system reactions.^56,57 The neuroendocrine component of the hypermetabolic response includes raised blood concentrations of stress hormones: the glucocorticoid cortisol (also a catabolic hormone/steroid; released from adrenal cortex) and the catecholamine epinephrine (from the adrenal medulla).^58,60 The immune component is multifaceted and diffuse, with a variety of hormones and proinflammatory cytokines bridging the innate and adaptive immune response.⁷⁷ Over time, the immune-inflammatory response can lead to a systemic inflammatory response syndrome (SIRS) and, if severe enough, post-injury multiple organ failure (MOF) and compensatory anti-inflammatory response syndrome (CARS).^57,59,77,78

  This phase’s collective actions are characterized by a hyperdynamic, hypermetabolic response, with increased oxygen consumption (see Fig. 60-2), increased energy expenditure, increased body temperature, and increased heart rate as well as proteolysis, glycogenolysis, and lipolysis.^56,65 The resultant accelerated catabolism causes breakdown of skeletal muscle, with negative nitrogen balances and loss of body weight (referred to as auto-cannibalism).^58,79 There is mobilization of stored carbohydrate (glycogen via glycogenolysis) and peripheral insulin resistance leading to hyperglycemia.^64,67 Additionally, there is mobilization of fat (triglyceride via lipolysis) with resulting increase in the plasma concentration of fatty acids and triglycerides^64,67; the rate of fat oxidation is twice that in a normal human.⁷⁵

  Overall, it is the initiation of the innate cellular immune system (monocytes, macrophages, neutrophils, endothelium) coupled with other immunological changes (activation of complement and coagulation cascades, with resultant release of myriad mediators, including cytokines) which feed the hypermetabolic process.⁶¹ In addition to driving the metabolic response, these factors also drive microvascular thrombosis, mitochondrial dysfunction, cellular necrosis and apoptosis, and secondary remote organ dysfunction (see Fig. 60-3).⁶⁴

  The catabolic flow period lasts for at least 7 days, and at its most severe up to 3 weeks or longer (note that in burn patients the hypermetabolism can last up to two years).^61,67 The proportion of this inflammatory response is directly related to the intensity of the injury. This intermediate phase is also known as the immune phase (due to activation of the innate immune system) or the leukocytic phase.

  • Targeted metabolic therapy for the catabolic flow phase:

    The metabolic changes during this catabolic flow phase catalyze a redistribution of macronutrients and micronutrients (see Fig. 60-1). Labile reserves of protein (skeletal muscle) and fat (adipose tissue) are broken down to provide energy to more active tissue (liver and bone marrow) for host defense, visceral protein synthesis, and heat production.⁵⁸ These metabolic alterations in the severely injured patient need to be recognized and addressed during their initial and acute stages.^64,79 The hypermetabolic state increases overall kilocalorie energy requirements and the increased catabolism with skeletal muscle breakdown increases dietary protein requirements. Early enteral or parenteral nutrition has proven beneficial in this regard (discussed in detail below).

    Given the importance of the immune system in driving and maintaining the catabolic flow phase, nutritional therapies to directly alter and target immune function and immune mediators are in theory both logical and possible. Recommendations for glutamine, omega-3 polyunsaturated fatty acids, and other immune-enhancing supplements for trauma patients have been supported in the past. However, new data is changing the landscape of immunonutrition (discussed in detail below), and there is now true clinic equipoise with regard to its use.

    This phase’s hypercatabolic state is associated with severe complications related to hyperglycemia, hypoproteinemia, and immunosuppression.^58,64 These processes can lead to multisystem organ dysfunction, SIRS, and post-injury MOF.⁵⁹ For these reasons, early initiation of glucose protocols with sliding scale insulin are essential, as is attention to nutritional therapy.

• The anabolic flow phase:

  The anabolic flow phase gradually occurs as the patient’s post-traumatic metabolism shifts from catabolism to synthetic activities and reparative processes.⁶¹ This phase reprioritizes protein synthesis in the liver, known as the acute phase response. Mediating this phase is increased adrenal cortical hormone secretion as well as a variety of cytokines (IL-1, IL-6, tumor necrosis factor-α), which stimulate the liver’s synthesis of the acute phase reactants, including fibrinogen and CRP (C-reactive protein),⁶⁷ initially at the expense of constitutive proteins such as albumin.⁵⁸

  Eventually a convalescence is achieved, as the hypercatabolic syndrome is progressively downregulated with reduction of catabolic hormones (catecholamines, proinflammatory cytokines, cortisol, glucagon) and increase of anabolic hormones (insulin, growth hormones, insulin-like grown factor 1, anabolic steroids).⁵⁶ With time, there is an exponential increase in the levels of positive acute phase proteins and a decrease in levels of negative acute phase proteins.⁶¹

  This phase is also characterized by a return of oxidative metabolism, leading to angiogenesis in the injured tissues and organs, facilitating tissue repair and regeneration.⁶⁴ For this reason, the phase is also known as the angiogenic phase or the endocrine phase, as it is the endocrine functional system that facilitates oxygen transport.⁵⁶ With time, there is full recovery of the endocrine system (hypothalamic-pituitary-organ-hormonal axes), the nervous system (autonomic nervous systems), and the immune system (innate and adaptive).⁵⁶ These responses make possible the complex process of resolution of inflammation as well as a return to normal homeostasis.

Nutrient Utilization and Needs After Trauma and Injury: 7 Key Questions

Depending on the severity of the injury, traumatically injured patients are at risk for developing a hypermetabolic post-traumatic stress response (discussed in the last section). If the metabolic insults persist, the body goes into a hyperdynamic state, with breakdown of skeletal protein and rapid loss of lean body mass. Potential complications from this state of hypercatabolism associated with post-traumatic hyperglycemia, hypoproteinemia, immunosuppression, and the multitude of other effects include: onset of protein-calorie malnutrition; infectious morbidity; multi-organ dysfunction; prolonged hospital stays; post-injury multiple organ failure; and disproportionate death.^{33,59,80,81,82,83}

The inflammatory stress response can be broken down into three phases: ebb, catabolic flow, anabolic flow. Each of these phases induces distinct pathophysiologic changes that can require interventions to eliminate or minimize their untoward consequences.⁶¹ One of the most fundamental and important interventions is nutrition.^{61,79,80,84,85,86,87}

• Why? Why is nutritional support important?

  Early recognition of the hypermetabolic state and adequate early nutritional support are essential to not only meet the patient’s increased nutritional needs (and thus preserve lean body mass), but also to facilitate recovery and healing, restore the body’s capacity for optimal immune function, prevent oxidative cellular injury, attenuate the inflammatory stress response, and prevent complications.⁸⁰ In this sense, early nutrition has gone from supportive care to outright therapeutic care,³³ and can be thought of as “metabolic control.”^80,81,85

• Who? Who needs post-injury nutritional support?

  All trauma patients will benefit from nutritional support, especially early in the hospitalization in those who are severely injured or those with baseline malnutrition prior to the injury. The severely injured patients are at highest risk for developing a hypermetabolic state, and subsequent malnutrition.

  The metabolic response to trauma in clinical terms is an “all or none” response: the patient with an injury severity score (ISS) of 18 is metabolically similar to the patient with an ISS of 50.⁷⁵ For this reason, some have advocated using an ISS greater than¹⁶ to identify severely injured patients who are at risk for hypercatabolism and malnutrition.³⁴ While this is certainly possible, more often identifying a severely injured patient is done by clinical judgment. It is these patients who need to be assessed for specific nutritional formulations with higher protein intake.

  There are some unique trauma patient populations with unique nutritional needs and requirements. These include traumatic brain injury (TBI) patients, burn patients, and others. Please see “Specialized Patient Populations” section below for details and recommendations. This section also has details on how to perform a nutritional assessment to identify patients with baseline malnutrition.

• When? When to implement nutritional support?

  Prior to starting any nutritional support, the end points of traumatic shock resuscitation should be achieved and the patient stabilized.^31,33,80,88 Once achieved, early (within 24–48 hours of injury) enteral nutrition should be started as soon as possible.^31,33 While there are different definitions of early (within 12 hours,⁸⁹ within 24 hours,⁹⁰ or within 48 hours^31,91 of injury or admission to ICU), in general within 48 hours or earlier is accepted. Early enteral nutrition is so fundamental to good patient management that it should be the final component of traumatic resuscitation.⁹¹

  The severely injured polytrauma patient who does not receive nutritional support in the first few days after the injury can develop worsening energy and protein deficits, which contribute to risk of complications.^80,81,82,92 Multiple prospective randomized controlled trials have shown that early nutrition can decrease infection rates, hospital lengths of stay, cost, and improve outcomes.^92,95 Trauma patients with an open abdomen without an associated bowel injury who were started on enteral nutrition once resuscitation was completed had decreased complications and improved survival (see Fig. 60-4).⁹⁶

• What? What should be used as nutritional support?

  Choosing the ideal nutrient formulations for injured and/or critically ill patients is increasingly complex. There are many options for both enteral and parenteral nutrition, from the basics to specialized formulations. Please see “Nutrition Intervention” section for details and specifics.

• Where? Where in the body to feed: GI tract or parenterally?

  Patients who have an injury, disability, or critical illness that will preclude their ability to initiate by mouth, oral feeding (aka feed themselves) beyond hospital day 5 should be started on enteral tube feedings as soon as safely possible, once resuscitated and stable.^33,34,80,96

  Early enteral nutrition via either gastric feeds or post-pyloric feeds are both acceptable.^{31,33,89,94,98,99,100} This can be achieved through either continuous or intermittent tube feeds, as discussed later in the chapter. The benefits of the enteral route as compared to the parenteral route include fewer infections (pneumonia; catheter related blood stream infection); decrease possibility of bacterial translocation; prevention of gut mucosal atrophy; avoid complications of parenteral nutrition; avoidance of complications of intravenous access for parenteral nutrition; reduced cost.^31,33 There is no mortality benefit to EN over PN.

  While the enteral route is preferred, there are situations when parenteral nutrition (PN) is indicated. If enteral feeds are contraindicated, have failed, or are not expected to be started for 3 days, then exclusive parenteral nutrition (PN) should be considered.^32,34,101 Note that the 3 days cutoff for initiating exclusive PN is controversial. The American Society for Parenteral and Enteral Nutrition (ASPEN) and the Society of Critical Care Medicine (SCCM) guidelines use a cutoff of 7 days to start PN in previously healthy patients prior to their critical illness and injury; however, in patients with baseline protein-calorie malnutrition and EN is not feasible, they do recommend early exclusive PN.³³ The European Society for Clinical Nutrition and Metabolism (ESPEN) uses a cutoff of 3 days.³²

  If enteral feeds will be inadequate for the first 3–10 days (inadequate defined as achieving only 25% of 24-hour kilocalorie goal), then one option is use of complementary PN, meaning the use of PN in addition to EN. This topic is also controversial. Complementary PN (aka supplemental PN; dual modality therapy; top-off TPN) is recommended by ESPEN³² but not by ASPEN/SCCM.³³ However, the ESPEN guideline was written prior to their publication in 2011 of a large, prospective, randomized controlled trial which found no benefit to early (day 3 of ICU stay) versus late (day 8) initiation of complementary PN.¹⁰²

  The need for supplementary PN must be interpreted with data demonstrating that trophic EN feeds (which by definition have a negative nitrogen balance) for 7 days in critically ill non–trauma patients have outcomes equivalent to goal tube feeds over the same time period.^103,105 Therefore, if a patient can tolerate even trickle tube feeds, achieving nitrogen balance with complementary PN is not needed. While somewhat controversial (ASPEN/SCCM will cite data demonstrating higher infectious morbidity and rates of ARDS when using complementary PN in patients already receiving 1000 kcal/d of EN¹⁰⁶; and ESPEN will cite data demonstrating a strong correlation between negative nitrogen balance and morbidity and mortality in critically ill patients),^107,108 at present, there is not sufficient evidence to make a best recommendation on complementary PN,^34,109 beyond the fact that is should not be started before hospital day 8.¹⁰²

  Enteral or parenteral modes of nutritional therapy are different means to the same end. In this manner, attention must be paid to the patient’s tolerance of one route and, if necessary, switching to the other route.

• How? How to deliver nutritional support?

  Please see “Nutrition Intervention” section for details and specifics on the delivery and administration of enteral nutrition, including access choices, monitoring, and complications.

• How much? How much energy and macronutrients are required

  • Energy = kilocaloric needs after trauma

    Most critically ill trauma patients have in common an increased metabolic rate. The hypermetabolic response coupled with increased protein catabolism create an amplified energy requirement in the severely injured patient. The increase in energy requirements may range anywhere between 30 and 70% above normal, though even the most experienced clinicians are unable to predict the extent to which trauma or injury will amplify an individual’s energy requirements.⁵⁸

    Based on studies calculating nitrogen losses, needs are increased approximately 30% in major injury, 50% in sepsis, and 75–100% with severe burns (see also Fig. 60-2).⁵⁸ Translating these increased metabolic rates into higher kilocalorie requirements is a bit more nuanced. This is because increasing evidence suggests that critically ill patients have lower energy requirements than expected. For example, while injury and infection increase REE, in most cases the increase is modest and largely offset by immobility.¹⁰

    Therefore, the old strategy of meeting or exceeding energy requirements after a major trauma compounds the metabolic alterations of the stress response, and worsens outcomes.¹¹⁰ A more modern nutritional doctrine is that over-nutrition has detrimental complications.^{31,32,33,34,111} For this reason the use of injury factors (which are not the same as “activity” factor multipliers) for the HBE to calculate EER are not recommended (an old dogma was to multiply the 24-hour kcal HBE BEE by factors for postoperative and/or injured patients, such as: 1.20 if elective surgery; 1.35 if trauma; 1.60 if major sepsis; 2.1 if major burn).¹¹²

    A nutritional support goal of 20–25 kcal/kg IBW/d is enough to be beneficial during the acute and initial stress response in the critically ill trauma patient.^31,110 This is in keeping with guidelines that highlight reaching at least 50% of total daily goal kilocalories over the first week of the hospitalization, if goal nutrition can’t be achieved.³³ During the anabolic recovery phase (aka anabolic flow period; convalescence) the aim should be to provide slightly more energy, from 25 to 30 kcal/kg IBW/d.³¹ Other guidelines recommend a daily kilocalorie increase of 40% above BEE, which translates into a nutritional support goal of 25–30 kcal/kg IBW/d.^31,32,33,34

    The ASPEN/SCCM guideline endorses both predictive equations as well as indirect calorimetry for calculating target energy goals, as does ESPEN. If these goal values cannot be achieved, trophic enteral feeds at lower rates (ranging from 10 to 30 cc/h) have huge benefits over starvation, and have outcomes that are as good as EN at goal.^103,104,105

    Finally, the question arises which body weight should one use in nutritional calculations in polytrauma and critically ill patients: ideal body weight (IBW), actual body weight (BW), lean body weight (LBW), or adjusted body weight (ABW). This was briefly mentioned in the first section of the chapter. The ESPEN guidelines strongly recommend using IBW for all weight-based calculations (“it is therefore wise to consider ideal body weight when calculating energy requirements”).^31,32,88,113 Using IBW avoids the pitfall of overfeeding patients. The ASPEN/SCCM guidelines use the actual BW for patients with a BMI less than 30, and IBW for those with BMI more than or equal to 30. Note that in patients with actual BW BMI less than 30, that approximates to the IBW, and thus IBW can be used without dire consequences.

  • Protein needs after trauma

    Protein is thought to be the most important macronutrient for wound healing, immune function, and preventing loss of lean body mass in the injured and critically ill patient.³³ The hypermetabolic, hypercatabolic state of post-traumatic stress induces a profound breakdown and redistribution of body protein (see Fig. 60-1); protein needs to be replenished and levels maintained.⁵⁸ If such needs are not appropriately addressed it can lead to ongoing erosion of lean body mass and negative nitrogen balances.

    In the midst of a severe inflammatory stress response, once normal synthetic reactions may require substantially different patterns of amino acid usage: proline for collagen synthesis, aromatic amino acids for synthesis of antibodies and acute phase proteins, and glutamine for rapidly dividing cells.¹⁰ In such conditions, amino acids that are not usually essential can become conditionally essential due to limited synthetic capacity.¹⁰ The amount and composition of protein required to maintain nitrogen balance in post-injury critically ill polytrauma patients may differ substantially from that in healthy subjects. For example, if loss of lean body weight is severe, adults can have a requirement for essential amino acids resembling that of a growing child due to the needs for tissue rebuilding.¹⁰

    During the acute stress response, a nutritional support goal ranging from 1.2 to 2.0 g protein/kg IBW/d will stem the loss of lean body weight and prevent negative nitrogen balances.^31,32,110 The ESPEN guidelines specifically recommend 1.3 to 1.5 g/kg IBW/d in critically ill trauma patients.^31,32 The ASPEN/SCCM guidelines recommend 1.5 g/kg BW/d if BMI less than 30, 2.0 g/kg IBW/d if BMI 30–40, and 2.5 g/kg IBW/d if BMI more than or equal to 40.³³

    Note that some guidelines use a nitrogen-based recommendation, and the conversion is 1 g nitrogen is equal to 6.25 g of protein. Some critically injured polytrauma patients will demonstrate such significant and rapid muscle losses that they have protein requirements three times the normal level, meaning closer to 2.5 g/kg/d.⁶¹ However, the desire to simply add supra-therapeutic levels of protein must be buffered with the fact that it will not prevent the hypercatabolic state in critically ill trauma patients.¹¹⁴

    The distribution of nutrition kilocalories among the macronutrients during the stress response is not firmly established. It should be adjusted to particular circumstances and for individual patients, keeping in mind the Acceptable Macronutrient Distribution Range (AMDR) (see Table 60-2).

    Standard recommendations call for calculation of protein kilocalories first based on a protein requirement of 1.3 g/kg IBW/d.^31,32 Then calculate the carbohydrate and fat energy distribution (see below).When calculating energy provision for artificial nutrition support by either enteral or parenteral nutrition, do not consider energy provided as protein as separate from energy given as nonprotein calories.

  • Carbohydrates needs after trauma

    Carbohydrates should constitute 50–70% of nonprotein calories.³⁴ See specifics on enteral and parenteral nutrition below.

  • Fat needs after trauma

    Fat should constitute 20–30% of nonprotein calories.³⁴ See specifics on enteral and parenteral nutrition below.

  • Water needs after trauma

    The impacts of dehydration are amplified in the critically ill and post-injury patient.⁵¹ Dehydrated trauma patients (those who have lost 7–10% of body weight as water) are more susceptible to fever, have increased cardiovascular strain and reduced tissue perfusion, and are at increased risk of death.⁵¹ Euvolemia should be maintained as discussed in the “Normal nutritional states of health” section.

Nutritional Intervention

Choosing and constructing the ideal nutritional therapy for injured and critically ill patients is increasingly complex. Expanded knowledge of the pathophysiology of the post-traumatic stress response as well as critical illness, coupled with the growing field of nutritional sciences, have made the possibility of disease-targeted nutrition a near reality. Enteral and parenteral formulas today are expected to not only provide balanced nutrients to meet energy requirements, they are also supposed to modulate the immune system, enhance neuroendocrine function, mitigate the hypermetabolic response to injury, and offset post-injury catabolism.

In metabolically stressed polytrauma patients, the anabolism-catabolism balance becomes severely weighted toward catabolism, leading to rapid depletion of body tissue stores and critical protein elements, such as immunoglobulins. This is characteristic of protein-calorie malnutrition. The primary goal of nutritional intervention is therefore to minimize the net negative energy and protein balances, and their negative downstream consequences, while appreciating that lean tissue loss is unavoidable in severe trauma patients even with aggressive nutritional therapy. The secondary goal, which is increasingly controversial, is to target immune and neuroendocrine function via pharmaconutrition.

Before reading further, please ensure you have read the last section entitled “Nutrient utilization and needs after trauma and injury: 7 key questions.” That section addresses the why, who, when, what, where, how, and how much of trauma patient nutritional support. For additional resources, multiple medical, surgical, trauma, and critical care organizations have developed and published nutrition guidelines, which are of benefit, as are their websites:

• Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN)³³ (this guideline will be updated in late 2015)

• European Society for Clinical Nutrition and Metabolism (ESPEN)^31,32,88,113

• Canadian Critical Care Society (CSCN)⁹⁰

• Eastern Association for the Surgery of Trauma (EAST)⁸⁴

• Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE)³⁴

• German Association for Nutritional Medicine (DGEM)^115,116

If nutritional requirements are properly attended to, the polytrauma patient should get the right type of nutritional substrate, in the right amounts, at the right time. This is easier said than done, however, as nutrition and nutritional science is a modern, complex, and ever-changing field of medicine. Nutrition, after all, is not intuitive,¹¹⁷ and nutritional assessments and interventions demand that one’s clinical knowledge is up-to date.

Enteral Nutrition

Meeting the increased energy requirement with early enteral nutrition is essential to the adequate care of the injured patient.⁶⁴ Prospective, randomized controlled trials have clearly proven the positive effect of early enteral nutrition in the polytrauma patient, with decreased posttraumatic infection rates, a shorter hospital length of stay, and improved morbidity and mortality.^92,93,94,95 See Fig. 60-5 and Fig. 60-6 for examples of EN algorithms.

• Patient selection

  All patients should ideally receive nutritional support within 24–48 hours of injury. Before starting enteral feeds, a thorough history (including past medical and surgical) and physical exam, should be completed. Conditions such as heart, liver, and/or kidney disease as well as alcoholism and malnutrition will impact the approach to enteral feeding, as will key operative history such as short gut or gastric bypass. Please see “Special Patient Populations” section for more specifics; particularly important is the section “Patients with baseline malnutrition or high nutritional risk.”

• Meeting nutritional requirements by enteral route

  How to meet the macronutrient and micronutrient requirements of both healthy and critically ill, hypermetabolic trauma patients was discussed earlier in the chapter.

• Enteral formulas and choices

  Highly sophisticated enteral nutritional formulations were developed long ago as part of NASA’s space program.¹¹⁸ Back then the goal was to develop a diet that would leave no fecal residue. Such enteral formulas eventually became known as elemental diets, and while astronauts rejected them as tasteless, medicine has embraced them as revolutionary. And it is clear why: they can be given in defined concentrations, they contain all macro- and micronutrients, and some require very little enzymatic activity on the part of the gastrointestinal tract. Enteral nutritional formulas (aka artificial nutrition; chemically defined diets) today cover a full spectrum of products, many claiming pharmacologic effects in addition to standard nutrient delivery; hundreds are available.

  Choosing an appropriate enteral formula is mostly based on meeting the energy (kilocalorie) and protein requirements of the patient (these requirements are discussed at length earlier in the chapter). Other considerations include baseline nutritional status, electrolyte balance, digestive and absorptive capacity, disease and inflammatory state, ongoing or completed resuscitation, and comorbidities including cardiac, pulmonary, hepatic, and renal function.

  Enteral formulas are classified in three ways: standard, predigested, or specialized. There are many choices within each category. In general, if the patient has normal gastrointestinal function they can get standard formulas. If their GI function is compromised, then one should consider the predigested formulas. If they have significant baseline comorbidities, then a specialized formula can be considered; the specialized formulas are for both normal and abnormal GI function.

  • Standard formulas

    Standard formulas (aka polymeric formulas) have intact protein with balanced amounts of macronutrients. Their nutrient compositions are meant to match what is recommended in healthy individuals (within the Acceptable Macronutrient Distribution Range; see Table 60-2). They come in various kilocalorie concentrations (called kilocaloric density, ranging from 1.0 kcal/mL to 2.0 kcal/mL), which translate into higher or lower water content formulas. They are made with and without fiber supplementation; the fiber can be soluble and/or insoluble. The sources of carbohydrates, proteins, and fats are variable. Standard formulas require complete digestive capacity, as they have proteins in their original, natural form. These formulas are often much cheaper than others.

    For stressed polytrauma patients with systemic inflammation, high-protein (aka high nitrogen) formulas are necessary, meaning they usually have a nonprotein calorie to nitrogen ratio of 70:1 to 100:1 (much lower than the usual 150:1 ratio).³³ Additionally, two sources of energy are believed to benefit high-stress situations: medium-chain triglycerides (MCT) and branched-chain amino acids (BCAA).

  • Predigested formulas

    Predigested formulas are designed for patients with decreased absorptive capacity that need predigested nutrients, thus requiring less enzymatic activity by the GI tract and leaving no residue behind. The protein source in these formulas has already been broken down into either free amino acids (in the case of elemental formulas) or short peptides (in the case of peptide-based formulas, with either dipeptides or tripeptides). These formulas are also called hydrolyzed or partially-hydrolyzed formulas, as well as elemental or semi-elemental formulas.

  • Specialized formulas

    Specialized formulas are designed for a variety of clinical situations and conditions. These formulas can be generally categorized as either disease specific formulas or immune-modulating formulas (IMFs), though there is overlap.

    • Disease specific formulas

      The disease specific formulas are specially designed for renal disease, liver disease, diabetes/hyperglycemia, pulmonary disease (COPD, ARDS), and hypoallergenic patients. They can be useful for the stressed polytrauma patient with significant comorbidities.

    • Immune-modulating formulas

      Pharmaconutrition is the practice of using both nutrition and nutritional supplements as pharmaceuticals, namely with the intention of improving an outcome or curing a disease. An arm of pharmaconutrition is immunonutrition: the practice of using the diet to affect both the nutritional and the immune status of a metabolically stressed patient.⁵⁸

      The role of immune-modulating formulas (IMFs; aka immune-enhanced nutrition) was, in the recent past, considered routine clinical care for critically ill trauma and surgery patients.^31,88 As of today, however, it is more controversial,⁶¹ as the data on the true benefits of immunonutrition is changing rapidly. Part of the difficulty in interpreting this literature is that supplement dosing, timing, and route of administration are not standardized, the supplements can be given alone or as part of a combination therapy, and the patient-populations are heterogeneous.¹¹⁹ In short, at present there is true clinical equipoise with regard to immune-enhanced nutrition.

      The guideline from ASPEN/SCCM³³ strongly supports the use of IMFs in trauma and surgical ICU patients (though these guidelines were published in 2009; an updated guideline with new recommendations is scheduled to be published in late 2015). In several meta-analyses, adding immunomodulating nutrients to enteral feeding formulas was associated with reduced infectious complications and improved recovery compared with standard enteral nutrition. IMFs have therefore gained widespread use in severely injured polytrauma patients. Supplements that have been researched include arginine,^120,121,122 glutamine,^123,124 omega-3 polyunsaturated fatty acids,¹²² nucleic acids,¹²⁵ and micronutrient antioxidants (such as selenium),¹²⁴ among others.

      The most recent ESPEN guideline, on the other hand, has concluded there is no general indication for administering immune-modulating nutrients to critically ill patients.³¹ Two recent studies support the ESPEN stance: both the 2013 REDOX study of glutamine and antioxidants¹²⁴ as well as the 2014 MetaPlus Trial of high protein IMF¹²⁶ show an increased risk of mortality with IMFs compared to standard high protein formulas. While in theory glutamine, arginine, nucleic acids, omega-3 polyunsaturated fatty acids, selenium, and antioxidants should help as immunonutrition; in practice their use may be harmful.

  • Enteral access

    Multiple access options exist for the administration of enteral nutrition. They can generally be divided into either temporary (aka short term) or long term feeding access devices.

    • Enteral access devices and options

      Temporary access devices are one of two types: prepyloric or postpyloric. Prepyloric options including simple nasogastric tubes or smaller diameter feeding tubes placed into the stomach. Postpyloric tubes are also inserted through a nostril, though they are placed past the pylorus and into the duodenum or jejunum.

      Long term access devices are also one of two types: prepyloric or postpyloric. Prepyloric tubes are gastrostomy tubes; they mainly differ by their physical characterisitics and the method by which they are inserted (percutaneously, laparoscopically, or open). Postpyloric tubes can originate in the stomach (combination gastric-jejunostomy tube) or in the jejunum (jejunostomy tubes).

    • Indications for enteral access devices

      In general, there are few contraindications to feeding the stomach. There is no good data to advocate for postpyloric feedings as the delivery option of choice in polytrauma patients. Although it makes sense that postpyloric feeds would decrease the risk of aspiration and pneumonia, this has not been proven (please see below for in-depth discussion on gastric residual volumes).^127,128 Do not delay the initiation for enteral nutrition because of a lack of postpyloric access.

      The major indication for long term access (gastrostomy or jejunostomy tubes) is the anticipated inability of a patient to tolerate oral feedings beyond 1 month after the time of injury.

    • Patient positioning with enteral feeds

      Mechanically ventilated critically ill patients should have the head of the bed elevated to at least 30 degrees when receiving enteral nutrition³³; this is to decrease risk of aspiration and pneumonia.

  • Delivery and administration of enteral nutrition

    The delivery of enteral nutritional is achieved by either continuous or intermittent tube feeds. There is no data to support one method of delivery as superior to the other.

    Goal-directed continuous tube feeds (with a target goal of full kilocalorie nutritional support) are initiated by one of two strategies: the top-down approach (aka aggressive approach) or the ramp-up approach.¹²⁹ The top-down aggressive approach is akin to an hourly volume-based approach: immediately start the rate of tube feeding right on the maximal hourly goal, and de-escalate if needed. The ramp-up approach is more traditional, and involves initiation of tube feeds at a lower rate (often 15–25 mL/h) and increasing to the goal rate over a period of time.⁸⁰

    More recently, a third strategy has been espoused: trophic feeds. Trophic feeds do not target full kilocalorie support, but rather a lower level of both kilocalories and protein to provide the gastrointestinal (GI) tract the benefits of nutritional support (improved gut integrity, better contractility, increased brush border enzymes, restoration of the commensal bacteria)⁹⁷ without putting the patient at risk for aspiration, GI intolerance, or other complications of higher-volume feeds. With trophic feeds the rate is set low (10–20 mL/h, representing only 15–25% of goal kilocalories) and kept low for days; it can be thought of as a much delayed ramp-up to goal.

    Studies comparing these methodologies of continuous tube feeds have failed to demonstrate improved outcomes with increased amounts of enteral kilocalories via the aggressive approach compared to underfeeding with a trophic approach.^103,105 However, trophic feeds were not shown to be superior to a regimen of full target feeding. Additionally, these methods have not been studied in trauma patients, meaning patients with a hypermetabolic response getting trophic feeds may have ongoing erosion of lean muscle mass resulting in impaired recovery and worse clinical outcomes.⁹⁷ As such, iatrogenic underfeeding with trophic feeds appears to be safe in the very short-term, though timely advancement to goal remains the aim of early nutritional therapy in polytrauma patients.

    Trophic feeds by definition mean that the patient is getting less than goal energy requirements and less than goal protein requirements (typically 15–25% of goal). A fourth strategy is permissive underfeeding, when the patient gets goal rates of protein requirements but restriction of non-protein kilocalories. Recent studies have shown promise with permissive underfeeding in comparison to full feeding in critically ill patients,¹³⁰ though earlier studies lack both internal and external validity.⁹⁷

    From a practical standpoint, there are key considerations to choosing a strategy. One is that hypertonic enteral formulas will not be well tolerated if started at full volume and full concentration. A gradual buildup is necessary (over days) for the GI tract to accept this unnatural source of energy, without severe diarrhea (and thus risk of dehydration). Another is that the jejunal route may require more patience before full strength is tolerated, as the jejunum can be sensitive to tonicity, fat concentrations, and protein sources. Additionally, gastric feeds can be higher tonicity, with higher administration rates, and given as bolus feeds—thus giving the provider more options for nutritional support.

    It is not natural for the gastrointestinal tract to be exposed to food/nutrition continuously for 24 hours a day. For this reason, there is a school of thought that interrupting continuous tube feeds for 4–6 hours a day makes them better tolerated by patients and is healthier for the gastrointestinal tract. In this manner, the full kilocalorie feeding regimen would be given continuously for only 18–20 h/d. There is at present no data to support this practice.

    Intermittent infusions (aka bolus feeds) are delivered at intervals (every 4–6 hours), with a large volume given at each interval (often 200–500 mL). Bolus feeds are well-tolerated with a prepyloric feeding tube, especially in the outpatient setting. Most inpatients are administered tube feeds continuously. Jejunostomy tube feeds are not well tolerated as intermittent feeds (due to abdominal pain, distention, and diarrhea), and therefore must be given continuously.

    • Prokinetic agents

      Prokinetic drugs, such as erythromycin and metoclopramide, can be used to promote motility to achieve effective administration of enteral nutrition.^33,34,131 These agents help in emptying the stomach and in tolerating EN, but have not been shown to improve or change outcomes.³³

    • Gastric residuals

      The practice of regularly holding or interrupting prepyloric enteral nutrition for elevated gastric residual volumes (GRV) in mechanically ventilated patients has long been practiced. The rational is that, if, during the initiation or maintenance of enteral feeding, a threshold GRV was reached (anywhere from 200 to 500 mL has been used), this was proof of gastroparesis, delayed gastric emptying, or gastrointestinal dysfunction, and warranted stopping the enteral nutrition. Recent randomized controlled trials have questioned this practice.^127,128 However, checking GRV is by no means a dead practice, especially in a surgical/trauma ICU with patients at high risk for GI dysfunction.¹²⁹ Current, up to date recommendations from both the German Society of Nutritional Medicine¹³² and the Canadian Practice Guidelines¹³³ recommend checking GRV, even with this latest data.

  • Monitoring

    Once tube feeds are initiated, patients need to be closely monitored. Monitoring for fluid balance and losses, metabolic and inflammatory status, positioning (of both patient and tube), and early detection of complications are all required. Blood glucose should be checked at least every 6 hours. Electrolytes should be checked daily, especially with increased GI tract losses. Trace element and vitamin levels should be checked only as clinical concern warrants.

    During acute illness, the short-term goals of feeding are to restore and maintain function, while limiting further loss of lean tissue. During the weeks of convalescence, the aim is to restore lean mass as well as function. Nitrogen balance may be indicative of loss or gain of body protein but is not a goal in itself. Nonetheless, in the absence of specific tests for adequacy of protein intake, some measure of nitrogen balance is useful in various clinical settings, since a prolonged state of negative nitrogen balance is not compatible with life.¹⁰

  • Complications

    While in general enteral nutrition is extremely safe, there are potential complications. The complications fall into one of two categories: access complications (either during insertion or mechanical) or diet related complications.

    • Access complications

      • Insertion-related

        Feeding tubes of various types can be placed at the bedside, by interventional radiology, by gastroenterologists, and surgically. Each of these methodologies has inherent complications. These include bleeding, infection, nasal damage, intracranial insertion, pulmonary insertion, and perforation. While real and significant, we will not highlight the multiple potential surgical complications of gaining feeding access (these operations include percutaneous endoscopic gastrostomy (PEG) tubes, laparoscopic and open gastrostomy tubes, and placement of jejunostomy tubes).

      • Mechanical

        Various mechanical complications relating to the tube itself can occur. The lumen of tube can get obstructed. This is often the result of poor maintenance, or lack of tube hygiene. Obstruction can be prevented with free water flushing protocols and ensuring no crushed medications are administered through the tube. Tubes can also be accidentally dislodged or removed and they can migrate. Over time, tubes can cause discomfort, erosions, fistulae, and strictures.

  • Diet related complications

    Diet related complications (aka formula related) are specifically associated with the enteral formula itself (including a host of metabolic issues) or to the unnatural process of being fed via a tube. These include aspiration, diarrhea and gastrointestinal intolerance, electrolyte disturbances, micronutrient deficiencies, hyperglycemia, hypertriglyceridemia, refeeding syndrome, malabsorption, hypertonic dehydration, hyperosmolar nonketotic coma, liver dysfunction, renal dysfunction, overfeeding, infection, bacterial translocation, pneumatosis intestinalis and necrosis, fluid overload, and hypoprothrombinemia (from vitamin K deficiency), among others.

Parenteral Nutrition

In the year 1968, Dudrick and Wilmore proved—first in beagles, and later in a newborn girl with intestinal atresia¹³⁴—that a patient could grow and meet their nutritional needs by receiving exclusive intravenous nutrition. Their discovery of what is now known as parenteral nutrition (PN; aka total parenteral nutrition, TPN; formerly referred to as hyperalimentation or hyperal) has greatly expanded the ability of physicians to treat malnutrition in patients who were otherwise not candidates for enteral feeds. In this section, we discuss when to use PN, who will benefit from PN, how to order and initiate the use of PN to meet the needs to the patient, and how to monitor patients on PN to ensure few complications with good nutritional support.

• Patient selection

  All patients should ideally receive early nutritional support within 24–48 hours of injury. As discussed in detail in the Where section above, parenteral nutrition (PN) should be prescribed if:

  • enteral feeds are contraindicated (usually due to nonfunctional gastrointestinal tract from dysmotility, discontinuity, ischemia, fistula, or obstruction)

  • enteral feeds have failed (either because of nonfunctional GI tract, or because enteral nutrition is not adequately or consistently achieving nutritional goals)

  • enteral feeds are not expected to be started for 3 days in the post-injury, inflammatory stress response patient or patient at high nutritional risk

  Contraindications to starting PN, even if one of the above requirements is met, are ongoing resuscitation, shock, and/or high dose vasopressors. Nutritional therapy is vitally important, but it is never an emergency.

• Meeting nutritional requirements by parenteral route

  How to meet the macronutrient and micronutrient requirements of the polytrauma patient with parenteral nutrition is discussed below.

• Initiation and delivery

  Once the decision to start PN has been made, two things must happen. First, central intravenous access must be obtained. Second, a prescription for the TPN must be written.

  • Access

    Central venous access, with a dedicated line not to be used for anything else, is fundamental to PN administration. Compulsive attention to sterile technique for both placement and maintenance will prevent complications. Parenteral nutritional preparations have very high tonicity (often >1000 mmol/L, and usually close to 2000 mmol/L), and are better tolerated centrally.

  • PN Prescription

    There are 5 steps to writing a prescription for PN. See Fig. 60-7 for an example of PN calculations.

    • Step 1: Total kilocalorie and fluid volume over 24 hours

      Total energy requirements for the critically ill polytrauma patient were outlined in the last section, specifically the 24-hour kilocalorie requirement and the distribution between the macronutrients. The one major difference between enteral and parenteral nutrition in terms of nutritional support is that a strategy of “permissive underfeeding” should be pursued at first with PN; to do this, 80% of total daily nonprotein energy requirement should be given at first.³³ This correlates with Fig. 60-7 step 1 (use IBW) and step 2 (24-hour kilocalorie requirement).

      Total fluid volume of PN preparations will vary depending on their clinical condition, with patients in the immediate postresuscitation hypercatabolic phase needing more. In general, patients need a minimum of 30–50 mL fluid/kg of actual body weight to maintain hydration; as discussed earlier in the chapter, in adult men this is 3.7 L and in adult women is 2.7 L. Additionally, when initially starting PN delivery, volumes may be lower over the first few days (please see “Administration & Delivery” below). This correlates with Fig. 60-7 step 5 (fluid needs).

    • Step 2: Amino acids and protein

      Next is to calculate protein requirements and their contribution to total energy requirements. As noted earlier, 1.3 g/kg IBW/d is recommended in critically ill trauma patients,^31,32 and no more than 2.0 g protein/kg IBW/d.^31,32,110 Simply adding huge levels of protein will not prevent the hypercatabolic state in critically ill trauma patients.¹¹⁴ This correlates with Fig. 60-7 step 4 (nitrogen/protein needs).

      With PN, protein is delivered in the form of a balanced amino acid mixture of both essential and nonessential amino acids. The contribution of these amino acids, including branched-chain amino acid (BCAA), is variable. In septic patients, for example, TPN fortified with BCAA at high concentrations (0.5 g/kg/d or higher; up to 45% of total protein) has been shown to lower morbidity and mortality when compared to standard TPN.¹³⁵

      Supplementation of PN solutions with immune-enhancing amino acids is controversial and in flux. While at one point it was considered standard of care, more recent data is questioning that practice (see Enteral Nutrition section above for detailed discussion). For example, TPN solutions enriched with glutamine have been shown to increase jejunal mucosal weight and nitrogen levels, decrease atrophy of intestinal villi, reduce hepatic steatosis, reduce pancreatic atrophy, and decrease gut bacterial translocation.⁶¹ However, two large multicenter randomized controlled trials published in 2013 and 2014 found that ICU patients with multisystem organ failure receiving immunonutrition had significantly increased risk of death.^124,126

    • Step 3: Amounts of dextrose and lipids

      The next step is to outline the nonprotein kilocalorie distribution between the two major energy sources with PN: dextrose and fat (note that proteins as amino acids also provides an energy source, but at much lower amounts). Most kilocalories will come from carbohydrates, which are convenient and safe,³² and only a small amount of fat emulsion to provide the essential fatty acids. This correlates with Fig. 60-7 step 3 (dextrose and lipid needs).

      The protein:fat:glucose kilocaloric ratio in surgical patients should approximate to 20:30:50%, respectively.^31,32 The common three-in-one or two-in-one formulations will therefore need to be modulated. The three-in-one PN regimen contains all three macronutrients: typically 10–15% energy as protein, 30–45% as fat, and 35–55% as carbohydrate. A two-in-one regimen contains no fat (fat is given separately), and has 15–25% energy as protein and 75–85% as carbohydrate.

      Dextrose in parenteral nutrition should provide 50–70% of the daily energy requirements. A basal requirement is estimated to be roughly 2.0 g dextrose/kg IBW/d,³² much of this for brain metabolism, which oxidizes glucose at a rate of 100–120 g/d. During the stress response, the hypermetabolic state creates oxidative limits of energy utilization; for this reason, dextrose should not exceed 5 g/kg IBW/d.⁸⁴ If exceeded, this can lead to overfeeding and fatty liver. One method to monitor overfeeding is to check a respiratory quotient (RQ) by indirect calorimetry. The RQ is the ratio of CO₂ production to O₂ consumption. Excessive CO₂ production is evidence of overfeeding with carbohydrate, will drive the RQ greater than 1. With an elevated RQ, increased kilocalorie contributions from fat should be considered (as can happen in patients with pulmonary failure as well) as fat metabolism generates less CO₂.

      Fat emulsions in parenteral nutrition should provide 30–50% of the daily energy requirement; total dose of PN fat should be in the range of 1.0–2.0 g/kg IBW/d.³² Fat emulsions are usually in the form of long-chain triglycerides (LCT), though in the polytrauma patient it is best to use a mixture of both LCT and medium-chain triglycerides (MCT).³² As discussed previously, during the stress response MCT are preferred, as they do not exert negative effects on neutrophil and macrophage function or hinder the reticuloendothelial system.

      During the systemic inflammatory stress response, the addition of intravenous fish oil to the lipid emulsion, which provides omega-3 fatty acids (both eicosapentaenoic acid (EPA) and docosohexaenoic acid (DHA)), has been shown to mitigate multiple aspects of the inflammatory response.³² While much has been written about the metabolic benefits of omega-3 polyunsaturated fatty acids in fish oils (they have been shown to decrease ICU length of stay and are recommended in Europe),³² they are not available for parenteral nutrition in the United States (thought they are recommended for and available in enteral nutrition).^31,33

      If central access is not possible, PN preparations with very limited kilocaloric intake, primarily derived from fat, can be given into the peripheral vasculature. This is known as peripheral parenteral nutrition (PPN).

    • Step 4: Electrolytes, vitamins, and trace elements

      The major issue in specifying amounts for electrolytes, vitamins, and trace elements is their contribution to osmolar load. While daily requirements should be met,³² amounts should not exceed that level unless indicated for other reasons.

      Supplementation of PN solutions with immune-enhancing and antioxidant micronutrients is also controversial and in flux. During the hypermetabolic stress response, there is an increased need for vitamins and trace elements, but just how much of an increase is not well defined.

    • Step 5: Medication additives

      Certain medications can be added to parenteral nutritional formulations to simplify what is often a long list of IV and enteral medications in the critically ill patient. Examples include proton pump inhibitors and insulin.

  • Administration and delivery

    PN cannot be started at full goal intake from day 1; rather, the rate of administration must gradually increase over a few days to ensure tolerance. The factor limiting immediate goal delivery is glucose and the risks of hyperglycemia.

• Monitoring and complications

  Following a patient on PN involves monitoring the metabolic response to the infused nutrients and anticipating or preventing such complications. The major complication is hyperglycemia, and therefore glucose control and monitoring blood sugar levels is of paramount importance.^32,33 A high-risk period is while the volume and glucose load are being increased, before steady levels of administration have been reached. Glucose management can be compounded in diabetics, septic patients, or those on steroids. Hyperglycemia can lead to a hyperosmolar coma, which should be avoided at all costs. Insulin administration may be necessary.

  By its very nature, that aim of PN is to induce an anabolic state (occurs eventually in the hypermetabolic, hypercatabolic polytrauma patient). As such, serum electrolytes will need regular daily monitoring. Patients are at high risk for hypokalemia, as well as alterations in phosphate, calcium, and magnesium. Micronutrient and essential fatty acid deficiencies can also develop. Tonicity and acid/base balance need monitoring as well; TPN solutions have a pH of 4 to 5, and can be balanced by the addition of more bases, such as sodium or potassium acetate. Bloodstream infection and complications from venous access (such as venous thromboembolism) are always a threat. Lastly, while not major issues in the short term, over the long term liver dysfunction and hypertriglyceridemia are major concerns.

  In time, the goal is to transition the patient off of the PN and onto EN. While patients are on PN, EN can be gradually introduced. Once more than 60% of total daily kilocalorie requirements are being delivered enterally, PN can be stopped.³³

Special Patient Populations

• Infants and children: Please see The Pediatric Patient chapter for full specifics on meeting the nutritional needs of the pediatric injury patient.

• Geriatrics: Please see The Geriatric Patient chapter for full specifics on meeting the nutritional needs of the elderly injured patient.

• Obese patients: The energy requirement for critically ill and injured obese patients (BMI > 30) is lower than that for a nonobese patient, and should not exceed 70% of total daily 24-hour energy requirements. Rationale behind this is to achieve some degree of weight loss in this patient-population, which may in turn increase insulin sensitivity and reduce the risk of comorbidities.³³ This translates into target kilocalorie requirements of 22–25 kcal/kg IBW/d.^33,34,111 Protein requirements for BMI of 30–40 are in the range of 2.0–2.5 g protein/kg IBW/d; if BMI more than 40, then less than 2.5 g protein/kg IBW/d is required.³³

• Patients with baseline malnutrition or high nutritional risk: Malnutrition is common: it is estimated that up to 40% of hospitalized patients fit the diagnosis.^8,9 It occurs for two major reasons: because of a patient’s primary underlying baseline condition (before they were admitted to hospital, such as alcoholism or malignancy) or because they do not receive adequate nutritional intake for prolonged periods of time (typically while patients are hospitalized, such as post-injury or postoperatively). Malnutrition is associated with worse outcomes, including infection (pneumonia, abscess, and sepsis), respiratory failure, poor wound healing and pressure ulcers, increased length of hospital stay, and death. These patients are at huge risk for complications if they become critically ill, and often need slightly increased energy requirements, especially in the initial and acute phase of their injury.

  A baseline nutritional risk assessment must be made and subsequently used to guide nutritional therapy. Determining the nutritional status of trauma and critically ill patients can be challenging, but knowledge of baseline malnutrition and malnourishment is exceptionally valuable^136,137: those patients at moderate to severe nutritional risk are most likely the benefit from early nutrition and most likely to be harmed by iatrogenic underfeeding.³³ Validated scoring systems for nutritional risk include the NUTRIC score (Nutrition Risk Score in ICU)^138,139 as well as the NRS 2002 (Nutritional Risk Screening 2002 tool).¹³⁶ Randomized controlled trials have shown that nutritional intervention in patients identified to be undernourished or at high nutritional risk improves outcomes.^140,141

• Alcoholics: Alcohol is a major cause of malnutrition; from 20 to 60% of patients with alcohol dependence will be malnourished. This has major implications for the polytrauma patient-population. These patients often need significantly increased energy requirements, especially once stabilized: kilocalorie goals are 35–40 kcal/kg IBW/d and protein intake of 1.2–1.5 g/kg IBW/d.

• Spinal cord injury patients: Please see the Vertebrae and Spinal Cord chapter for full specifics on meeting the nutritional needs of the spinal cord injury (SCI) injury patient. In quadriplegic patients daily energy requirements are met with 20–22 kcal/kg IBW/d; in paraplegic patients it is a bit higher at 23–24 kcal/kg IBW/d.^34,142

• TBI patients: Please see the Injury to the Brain chapter for full specifics on meeting the nutritional needs of the TBI injury patient.

• Burn patients: Please see the Burns and Radiation chapter for full specifics on meeting the nutritional needs of the burn injury patient.

• Renal patients: In patients with acute kidney injury (AKI; meaning non-traumatic acute renal failure), there are multiple adjustments that should be considered to daily nutrition, especially parenteral nutrition. These include decreasing the grams of protein if blood urea nitrogen is more than100 mg/dL; decreasing magnesium, potassium, and phosphorus; increasing acetate; decrease overall kilocalories if on peritoneal dialysis; decrease fat kilocalories if triglycerides levels high; maximally concentrate all solutions.

• Intubated patients: In intubated patients avoid overfeeding to prevent excessive CO₂ production (which will make weaning off of the ventilator difficult), and try to maximally concentrate all solutions. In patients with overfeeding, indirect calorimetry will demonstrate a respiratory quotient (RQ) more than 1.

• Low flow states and hypoperfusion: Historically, enteral nutrition has been avoided in patients in low flow states because of the risk of worsening intestinal mucosal ischemia during periods of hypo-perfusion. This practice is evolving, as there is evidence to support the safe and beneficial use of trophic feeds even when a patient is in nonrefractory shock on low to moderate dose vasopressors.^104,143

• Hepatic patients: In patients with liver dysfunction, there are multiple adjustments that should be considered to daily nutrition, especially parenteral nutrition. These include decreasing protein levels in patients with encephalopathy; using branched-chain amino acids (BCAA) if encephalopathy unresponsive to medical treatment or is worsening; use both carbohydrate and fat to meet energy requirements; provide 150 g carbohydrate per day; maximally concentrate all solutions.

• Preoperative patients and holding tube feeds: Stopping tube feeds at midnight prior to operative interventions and diagnostic tests is routine practice in critically ill patients. It is thought to decrease the risk of aspiration when the patient is in the supine or prone position during the operation, and therefore at risk for aspiration. This is of particular concern in the polytrauma patient, as they are frequently in the operating theatre for a multitude of reasons at the start of their hospitalization, and thus tube feeds are frequently interrupted. Regularly stopping tube feeds at midnight leads to patients receiving at most 50% of goal energy requirements from one day to the next.¹⁴⁴ One study in burn patients found that those randomized to have tube feeds continued during their operative debridement (as compared to those who had EN stopped at midnight) had statistically fewer wound infections and reduced caloric deficits.¹⁴⁵ The ESPEN guideline for enteral nutrition in surgical patients does not endorse stopping liquid diet or tube feeds until 2 hours prior to operation.⁸⁸

Most feeds contain adequate electrolytes to meet the daily requirements of sodium, potassium, calcium, magnesium, and phosphate, although specific requirements can vary enormously. Malnourished or metabolically stressed individuals often develop electrolyte derangements.

Sodium and Disorders of Water Balance

Sodium and chloride are necessary to maintain extracellular fluid volume and plasma osmolality.^39,51 The most common electrolyte problems noted in trauma patients are derangements in sodium. While diabetes insipidus or inappropriate ADH may occur with head injuries, producing hypernatremia and hyponatremia respectively, the most common cause for abnormalities in sodium levels is an excess in sodium administration, fluid restriction in closed head injury patients, or administration of large volumes of fluid containing low sodium. In the first case, prolonged use of normal saline or lactated Ringer’s as a maintenance fluid in association with other hidden sources of sodium administered through multiple antibiotics, H₂ blockers, etc, in saline produces a gradual and progressive hypernatremia. Many antibiotics contain large amounts of sodium, and since specific admixtures for medications are rarely ordered, intravenous “piggybacks” can reach 2–2.5 L/d in some patients. If this is administered in normal saline, hypernatremia develops. Likewise, if medications are mixed in 5% dextrose and water, significant hyponatremia develops.

Assessment of volume status in concert with the low serum sodium concentration will usually identify the patient as hypovolemic, isovolemic, or hypervolemic. Hypovolemic patients usually respond to normal saline or lactated Ringer’s infusions. If losses of fluid are chronic and similar to serum (eg, ileostomy losses), additional sodium may be needed in the nutrient solutions. Isovolemic, hyponatremic patients often need little treatment beyond increasing the sodium content in intravenous fluids. In severe cases where urine sodium is elevated at 100–200 mEq/L, restriction of free water is necessary by decreasing fluid administration and concentrating the nutrient solution. This problem is most commonly seen with severe head injury or pneumonia and resolves as the patient recovers. Hypervolemic, hyponatremic patients should have nutrient formulas concentrated as much as possible. Other therapy such as diuretics may occasionally be needed.

A less common cause of hyponatremia after trauma is inappropriate ADH secretion. It is usually associated with central nervous system (CNS) effects induced by head injury, meningitis, subarachnoid hemorrhage, anesthetics, meperidine, carbamazepine, or tricyclic drugs. In addition, a decrease in the vascular volume, secondary to use of diuretics in patients who are on high levels of PEEP or have large fluid losses from the GI tract, open abdominal wounds, etc, can also lead to increased ADH secretion and increased sodium loss. Typically, serum chloride concentrations decrease with the hyponatremia, and a hypokalemic metabolic alkalosis with a high serum bicarbonate occurs, especially when diuretic-induced. The diagnosis of inappropriate ADH is made by a combination of hyponatremia, a decrease in serum osmolality, a urine osmolality that is elevated relative to serum osmolality, a urine sodium greater than 20, and, if measured, an increase in ADH. Because of the effect of ADH on the kidney, water is absorbed without sodium so that urine sodium and tonicity are high relative to serum. The appropriate therapy is water restriction.

Hypernatremia is also relatively common in the critically ill trauma patient, especially in patients with severe head injury, where a mild hyperosmolar state is often used to decrease intracranial pressure. After bedside assessment, most of these patients can be categorized as hypovolemic, isovolemic, or hypervolemic. Patients with hypovolemic hypernatremia are usually treated with lactated Ringer’s solution first to ensure adequate organ perfusion, and then with solutions containing substantial free water (eg, D5W, 0.22% or 0.45% sodium chloride injection). During free water administration, it is appropriate for the sodium to be reduced in the nutrient solution. Patients with isovolemic hypernatremia usually need free water and sodium should be removed from the PN. Patients with hypervolemic hypernatremia should have intake minimized by concentrating the nutrient formula. Exogenous sodium should be eliminated from PN, medications, and other infusions to the extent possible.

Potassium

Potassium is the main intracellular cation in the body and is required for normal cellular function.^39,51 Hypokalemia is very common after trauma, especially in patients with normal renal function who require aggressive resuscitation with crystalloid. Loss of GI fluids rich in hydrogen and chloride aggravates this hypokalemia. Patients with prolonged nasogastric suction will lose considerable HCl resulting in metabolic alkalosis and substantial renal wasting of potassium. Drug therapy with loop diuretics, amphotericin B, antipseudomonal penicillins, and corticosteroids has been reported to aggravate renal wasting of potassium. Other drugs, such as inhaled β-agonists (eg, albuterol) and insulin drive potassium into the cell also resulting in hypokalemia in some patients. All the above conditions will require additional potassium added to the nutrient solution above the standard of 30–40 mEq/L that is commonly used in PN or present in enteral formulas. Occasionally, up to 120 mEq of potassium/L must be added to nutrient solutions of patients who were receiving three or four of the above-mentioned drugs to keep them in potassium balance.

Body potassium needs are not proportionate to serum levels. Each 0.25-mEq drop in serum potassium levels between 3.0 and 4.0 mEq/L represents a 25- to 50-mEq deficit in total body potassium. Between 2.5 and 3.0 mEq/L, each 0.25-mEq drop represents an additional 100- to 200-mEq deficit, which must be replaced to avoid precipitous drops with refeeding. Hyperkalemia is less common than hypokalemia after trauma, and is usually associated with compromise in renal function. In general, hyperkalemia from ARF warrants potassium removal from the nutrient solution. Once levels have decreased to 4.0 mEq/L, potassium should be added back in modest doses (eg, 10 mEq/L). Other causes of hyperkalemia are hemolysis of the blood sample and drugs known to cause this disorder, even when renal function is normal. Most laboratories will identify hemolyzed samples that do not require treatment other than repeat analysis. Heparin and trimethoprim have been reported to cause hyperkalemia in patients. Heparin is an aldosterone antagonist that causes sodium wasting and potassium retention. This drug–nutrient interaction occurs with both systemic and low-dose heparin, especially in patients with diabetes and chronic renal dysfunction. Trimethoprim is a component of the combination product of trimethoprim/sulfamethoxazole used frequently for gram-negative systemic infections. It is a weak diuretic with potassium-sparing activities. Patients who experience these interactions should have potassium decreased in the nutrient solution, even when renal function is normal.

Phosphorus

Phosphorus helps maintain a normal pH in the body and is involved in multiple metabolic and homeostatic processes.^39,51 Hypophosphatemia is a common metabolic complication of critically ill patients receiving nutritional support. While most practitioners add phosphorus to PN solutions routinely, several patient populations require greater amounts, including patients with a history of alcohol abuse, poor nutritional status pre-injury or chronic use of antacids or sucralfate. Even when serum phosphorus concentrations are monitored closely, hypophosphatemia occurs in approximately 30% of patients receiving PN. Treatment of hypophosphatemia is dictated by the severity, and intravenous replacement doses are most frequently used. The enteral route should be considered in mild cases of hypophosphatemia by adding 5–10 mL of Fleet’s phosphosoda to each liter of the enteral formula in patients requiring additional phosphate. In patients requiring both potassium and phosphate, potassium phosphate (usually 15–22.5 mmol/L) can be added to the formula. For isolated potassium depression, potassium chloride can be added to the enteral formula.

Hyperphosphatemia is much less prevalent than hypophosphatemia in trauma patients and is usually associated with renal compromise when it does occur. Phosphorus should be decreased or removed from the nutrient solution.

Magnesium

Magnesium is involved in more than 300 enzymatic processes in the body, as well as bone health and in the maintenance of intracellular levels of potassium and calcium.^39,51 The development of hypomagnesemia is underappreciated. Magnesium is rapidly depleted in stress, particularly when diuretics and antibiotics such as aminoglycosides are administered. Dysrhythmias, hypocalcemia (an unusual problem in trauma patients), and irritability are avoided with magnesium monitoring and appropriate treatment. Patients with a history of alcohol abuse or lower GI losses, such as diarrhea, are particularly prone to develop hypomagnesemia. Amphotericin B, aminoglycosides, and loop diuretics (and in addition cisplatin and cyclosporine) have all been reported to cause renal wasting of magnesium. Intravenous magnesium replacement therapy is usually necessary in patients with moderate to severe magnesium deficiency due to poor absorption of oral magnesium salts. Magnesium has a renal tubular threshold similar to glucose, so rapid administration over a short period of time will invariably result in high urinary losses.

Magnesium status should also be considered in evaluating a hypokalemic patient, as magnesium is an important cofactor for the Na/K-ATPase pump. It may be necessary to administer magnesium replacement therapy for low-normal serum magnesium concentrations in the presence of hypokalemia, because magnesium is an intracellular cation and serum concentrations may not accurately reflect intracellular status.

Hypermagnesemia usually occurs in association with renal dysfunction or failure. Magnesium should be removed from the PN of these patients.