Chapter 6 Metabolism in Surgical Patients

Ahmed Al-Mousawi, Noe A. Rodriguez, David N. Herndon

Metabolism involves a diverse range of chemical processes required to sustain life and enable growth, healing, development, reproduction, homeostasis, and adaptation and response to the environment. Through highly efficient metabolic pathways, nutrients are absorbed, transformed, and broken down to release energy. The nutritional status of an individual depends on an adequate diet, function of the alimentary tract, and physiologic condition. In surgical and critically ill patients, metabolic and nutritional processes may be impaired as a consequence of environmental, pathologic, or traumatic factors, leading to a need for nutritional supplementation to enable healing and recovery. Development and implementation of nutritional support represents one of the main advances of the last century that has led to improved patient care and surgical outcomes.

Over recent decades, major progress has occurred in our understanding of the physiologic response to injury, increasing focus on improved nutrition in surgical care. Catabolism of skeletal muscle protein has been recognized as a major factor contributing to adverse outcomes following major surgery and trauma. In 1905, Sneve ¹ described the catabolic response as metabolic exhaustion and emaciation seen in burn patients. Cuthbertson² studied the effects of long bone fractures in animal models, characterizing physiologic and metabolic responses into two phases: the early ebb phase and the flow phase. The former occurs the first several hours after injury, typically lasts 2 to 3 days, and is distinguished by reduced oxygen consumption (VO₂), glucose tolerance, cardiac output, and basal metabolic rate. The latter typically starts several days after injury, lasts days to weeks, and features catabolic breakdown of skeletal muscle, negative nitrogen balance, hyperglycemia, and increased cardiac output, VO₂, and respiratory rate.

In 1953 Cope and colleagues ³ correlated muscle wasting following thermal injury with a measured rise in metabolic rate. Moore’s book, in 1959,⁴ proposed the use of continuous feeding to attenuate proteolysis and muscle catabolism observed following trauma. Establishing the feasibility of long-term parenteral nutrition (PN) in the late 1960s, Dudrick⁵ recognized that malnourished surgical patients with a preexisting protein deficit were at increased risk of complications.

It was then shown that the hypermetabolic response seen in patients with major burns resulted in part from an increase in catecholamine serum levels and that the metabolic response could be attenuated by ambient temperature and pharmacologic means. Further studies showed that severe trauma and burns lead to a hypercatabolic response, with deleterious effects on various organs, and that the inflammatory response contributes to hypermetabolism and subsequent catabolism seen following severe injury (Fig. 6-1).⁶ Modulation of this hypermetabolic response through pharmacologic and nutritional interventions, alteration of the environment, and improved surgical management are cornerstones of advancing surgical care.

FIGURE 6-1 Metabolic response to injury and trauma.

Although widely quoted, the classic description of the ebb and flow response may not be apt for critically ill patients in a modern intensive care setting. A refined description has been proposed for these patients, who may suffer further insults from multiple operations or repeated bouts of sepsis (Fig. 6-2). The classic description may also oversimplify the array of responses that occur; these remain incompletely understood, particularly in the prolonged flow phase, which includes a short-term acute response and prolonged adaptive response.

FIGURE 6-2 A, Classic ebb and flow phases of the acute stress response. The metabolic rate initially falls below normal and then increases to supranormal levels before returning to normal. B, Ebb and flow revisited. In the population of chronically ill patients in critical care, the classic ebb and flow pattern is altered. Recurrent bouts of sepsis and other proinflammatory stimuli result in a fluctuating metabolic demand, which remains chronically elevated.

(Adapted from Ball S, Baudouin SV: Endocrine disorders in the critically ill: The endocrine response to critical illness. In Hall GM, Hunter JM, Cooper MS [eds]: Core topics in endocrinology in anaesthesia and critical care, Cambridge, England, 2010, Cambridge University Press, pp 126–131.)

The metabolic response to injury aims to restore homeostasis. It is characterized by changes in the flow of substrates among organs, increasing glucose and amino acid supply to the wound or site of injury to facilitate repair and healing. Neuroendocrine and inflammatory mediators of the stress response induce changes such as muscle proteolysis, leading to the release of amino acids, primarily alanine and glutamine. These are needed for protein synthesis at the site of injury and are also converted to glucose by hepatic gluconeogenesis. Glutamine serves as a fuel supply to the gut and is converted to alanine and ammonia, which are used by the liver or converted to urea. Hypermetabolism results in critically ill patients when the metabolic response is severe and prolonged, together with a hyperdynamic circulation, muscle catabolism, increased nitrogen loss, and glucose intolerance.

Nutritional Requirements

The primary goal of nutritional support is to provide an adequate energy supply and all the nutrients necessary to support life and function. Nutrients in the diet require ingestion, digestion, absorption, and regulation before the substrates released are used, stored, or expended for energy. The major components of the diet are carbohydrates, lipids, and proteins (Fig. 6-3). As a source of calories, 1 g of carbohydrate yields 3.4 kcal (16 kJ) of protein, and 4 kcal (17 kJ) yields 9 kcal (37 kJ) of fat. Fuel preferences differ across various types of cells; erythrocytes and neurons use glucose preferentially, muscle and cardiac myocytes can also use fat, and enterocytes and lymphocytes can metabolize the amino acid glutamine. Adaptation to different fuels can occur under circumstances of starvation.

FIGURE 6-3 Simplified overview of metabolic pathways.

At the cellular level, adenosine triphosphate (ATP) is the main source of energy that drives reactions and metabolic processes. Hydrolysis of three high-energy phosphate bonds within the molecule releases chemical energy that fuels cellular work. A continuous supply of ATP is needed; it is synthesized by reactions that use glucose, amino acids, and fatty acids to phosphorylate and recycle ATP from adenosine diphosphate and monophosphate.

Glycolysis is the energy-producing metabolic pathway within cells that converts glucose (six carbon atoms) into pyruvate (three carbon atoms), with net production of ATP and nicotinamide adenine dinucleotide (reduced form, NADH). In cells with mitochondria and sufficient oxygen, pyruvate is metabolized to carbon dioxide through aerobic metabolism, whereas if mitochondria or oxygen is lacking, glycolysis takes place anaerobically, producing lactate. Anaerobic metabolism occurs in cells during states of hypoperfusion, in muscle cells during bursts of increased activity, and in cells without mitochondria such as red blood cells, in which anaerobic glycolysis is the only energy-producing pathway.

Phosphorylation of ATP occurs in the cell cytoplasm during glycolysis (anaerobic, substrate level phosphorylation) and in mitochondria in the tricarboxylic acid (TCA) cycle. Oxidative phosphorylation of NADH and succinate, products of the TCA cycle, generates further ATP within mitochondria through aerobic respiration, a more efficient pathway than anaerobic glycolysis. Two molecules of pyruvate are produced from each molecule of glucose that enters glycolysis, yielding two ATP molecules. In comparison, a single molecule of glucose yields approximately 32 molecules of ATP through glycolysis, subsequent oxidation of pyruvate to acetyl coenzyme A (acetyl-CoA), and progress into the TCA cycle, which ends with oxidative phosphorylation of the products.

Lipolysis involves the hydrolysis of triacylglycerol (TAG) stored in adipose tissue to release fatty acids and glycerol. Although glycerol can be used by the liver to synthesize glucose, fatty acids cannot be used to synthesize glucose in humans. As a result, proteolysis occurs during periods of stress or prolonged starvation after depletion of glycogen stores, primarily through degradation of muscle protein, but also solid organs, to maintain glucose homeostasis.

β-Oxidation is the oxidative degradation of saturated fatty acids, whereby two carbon units are sequentially removed to form acetyl-CoA and electron donor molecules (NADH and FADH₂ [flavin adenine dinucleotide, reduced form]) used to generate further ATP by oxidative phosphorylation. Fats represent a dense source of calories because this process has an extremely high energy yield, with 129 molecules of ATP being formed from one molecule of the typical fatty acid palmitate.

Carbohydrate Metabolism

Carbohydrates are a primary source of calories and are divided into four groups: simple carbohydrates, which include monosaccharides (one sugar unit) and disaccharides (two sugar units); and complex carbohydrates, which include oligosaccharides (three to ten sugar units) and polysaccharides (>ten sugar units).

Carbohydrate digestion begins in the mouth with the action of salivary amylase, which hydrolyzes polysaccharide bonds in the amylose and amylopectin molecules that constitute starch. Breakdown continues in the gut by the action of pancreatic amylase and of the enzymes sucrase, lactase, maltase, and isomaltase from intestinal epithelial cells to yield monosaccharides. Bacteria in normal gut flora enable the breakdown of certain polysaccharides and starches, which humans lack the enzymes to digest, and help prevent the invasion of pathogenic strains in the intestine.

The products of intestinal digestion yield the monosaccharides glucose, fructose, and galactose. These sugars are rapidly absorbed and transported to the liver. Approximately 90% of portal venous glucose is removed from the blood by hepatocytes through carrier-facilitated diffusion. Carrier molecules on the sinusoidal domain of hepatocytes are capable of binding and transferring the sugars into the cytoplasm.

Glycogen is the stored form of carbohydrate in the liver and skeletal muscle. The liver plays a key role in processes that synthesize and degrade glycogen (glycogenesis and glycogenolysis), and in the endogenous synthesis of glucose (gluconeogenesis). Glycogen can be stored in the liver, in up to 65 g/kg of tissue, and is stored in muscle for its exclusive use. Hepatic synthesis of glycogen begins with a core composed of a high-density protein (glycogenin) and the action of a rate-determining enzyme, glycogen synthase. This enzyme is activated by insulin and glucose, both of which are elevated in the postprandial state, leading to elongation of the glycogen chain by the addition of glucose units. Conversely, glycogen synthase is inhibited by glucagon and epinephrine. During fasting, glycogenolysis leads to the release of glucose, with the rate-limiting enzyme glycogen phosphorylase activated by glucagon and epinephrine and inhibited by insulin. Glycogen stores are exhausted within 48 hours of fasting, and body protein stores must be mobilized to maintain adequate glucose supply to the brain.

In addition to glycogenolysis, glucose levels are maintained through the conversion of noncarbohydrate substrates by gluconeogenesis, which occurs primarily in the liver and, to a lesser extent, in the renal cortex. Substrates for this pathway include all amino acids except lysine and leucine, derived from the proteolysis of skeletal muscle, glycerol derived from the degradation of triglycerides (TGs) in adipose tissue, and lactate produced from anaerobic glycolysis (see Fig. 6-1). The enzyme-catalyzed reactions of the gluconeogenic pathway include the reversal of several steps of glycolysis and four irreversible reactions.

Lipid Metabolism

Lipids are hydrophobic molecules that include fatty acids, phospholipids, glycerolipids, sphingolipids, eicosanoids, and vitamins. They play key roles in cell structure and function, including energy storage and expenditure, formation of biologic membranes, and cell signaling. If lipids are not immediately used by cells, they can be stored in the form of TGs, the most potent caloric stores in the body, because 1 g of fat delivers 9 kcal (37.7 kJ).

Dietary TGs are unable to pass through the intestinal epithelial cells and must first be emulsified and hydrolyzed to monoacylglycerols or free fatty acids. This process is mediated by a mixture of lipases, biliary, pancreatic, and intestinal secretions from glands positioned along the gastrointestinal (GI) tract (tongue, stomach, pancreas, glycocalyx of intestinal wall).The stomach plays two important roles; it secretes gastric lipase, responsible for the digestion and absorption of up to 20% of total TGs, and it initiates the process of emulsification. Fat then enters the upper duodenum, 80% in the form of TGs and the rest in the form of partially hydrolyzed compounds. Emulsified TGs stimulate the contraction of the gallbladder and the release of bile and pancreatic fluid containing lipase, colipase, phospholipase A2, and cholesteryl esterase. Bile acids and colipase enable pancreatic lipase to act on TGs to produce diacylglycerols (DAGs), monoacylglycerols (MAGs), and free fatty acids.

Lipolysis occurs within the cytosolic lipid droplets of adipocytes, in which a series of lipases initiate the breakdown of TAG into free fatty acids and glycerol. Hormone-sensitive lipase (HSL) was until recently thought to be the only enzyme to hydrolyze TGs in adipose tissue. A second enzyme, adipose triglyceride lipase (ATGL), is now believed to catalyze the first step in the hydrolysis of TGs (Fig. 6-4).⁷

FIGURE 6-4 Regulation of lipolysis within adipocytes.

(Adapted from Ahmadian M, Wang Y, Sul HS: Lipolysis in adipocytes. Int J Biochem Cell Biol 42:555–559, 2010.)

In the postabsorptive state, adipose tissue releases free fatty acids and glycerol to the circulation for use as energy. Hepatic β-oxidation of fatty acids produces ketone bodies, acetoacetate, and 3-hydroxybutyrate, which can be used directly as fuel sources by cardiac muscle, skeletal muscle, and the renal cortex as well as cerebral tissue after a week of fasting. This switch of the central nervous system (CNS) during starvation, away from the primary use of carbohydrates to the use of ketone bodies as a fuel, represents a critically important adaptive step that has a secondary sparing effect on body protein.

Desnutrin-ATGL initiates lipolysis by hydrolyzing TAG to diacylglycerol. HSL hydrolyzes DAG to MAG, which is subsequently hydrolyzed by MAG lipase (MGL) to generate glycerol and three fatty acids. Fatty acids generated during lipolysis can be released into the circulation for use by other organs or oxidized within adipocytes. During fasting, catecholamines, by binding to Gαs-coupled β-adrenergic receptors (β-ARs), activate adenylate cyclase (AC) to increase cyclic adenosine monophosphate (cAMP) and activate protein kinase A (PKA). PKA phosphorylates HSL, resulting in the translocation of HSL from the cytosol to the lipid droplet. PKA also phosphorylates the lipid droplet–associated protein perilipin. Also, during fasting, glucocorticoids increase the expression of desnutrin-ATGL.

Protein Metabolism

Proteins are essential to the structure and function of every cell and participate in cell adhesion, signaling, and immunogenicity. The digestion of protein into peptides begins in the stomach through acid denaturation and the enzymatic action of pepsin. Digestion of peptides into tripeptides, dipeptides, and amino acids takes place at the level of the duodenum through proteases secreted from the pancreas and peptidases associated with the glycocalyx of the intestinal wall. Dipeptides, oligopeptides, and single amino acids are absorbed in the small intestine.

Human protein synthesis requires 20 amino acids; eight are termed essential amino acids because they cannot be synthesized de novo from other amino acids (10 if arginine and histidine are included as essential in infants) and must therefore be obtained in the diet. Six amino acids are termed conditionally essential amino acids because during childhood, illness, and other conditions, they may not be synthesized at rates that meet requirements and may therefore need to be supplemented. The remaining six are termed nonessential amino acids because they can be synthesized internally (Table 6-1).

Table 6-1 Amino Acids

AMINO ACID GROUP (ABBREVIATION)	FEATURES
Essential Amino Acids	Must be contained in diet because these cannot be synthesized
Valine (Val)	Branched-chain amino acid
Leucine (Leu)	Branched-chain amino acid
Isoleucine (Ile)	Branched-chain amino acid
Lysine (Lys)
Methionine (Met)
Threonine (Thr)
Phenylalanine (Phe)
Tryptophan (Trp)
Conditionally Essential	Conditionally indispensable because low synthesis rates may exceed requirements under certain conditions, especially in infants
Arginine (Arg)	Essential depending on health status of individual and for infants because it cannot be synthesized quickly enough
Histidine (His)	Previously considered essential for infants; now also considered essential for adults
Tyrosine (Tyr)	Can be synthesized from phenylalanine
Cysteine (Cys)	Can be synthesized from methionine
Glutamine (Gln)	Major energy source for intestinal mucosa
Proline (Pro)
Nonessential Amino Acids	Needs can be fully met by synthesis
Alanine (Ala)
Asparagine (Asn)
Aspartate (Asp)
Glutamate (Glu)
Glycine (Gly)
Serine (Ser)

Various tissues, including liver, muscle, kidney, lung, and adipose tissue, share regulatory roles in amino acid metabolism, although the catabolism of most essential amino acids takes place in the liver. However, the three branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are an exception, because these are poorly metabolized during first-pass metabolism in the liver and are degraded by skeletal muscle. The breakdown of BCAAs in muscle generates alanine and glutamine.

Alanine is released from skeletal muscle, in addition to lactate, during the anaerobic glycolysis of glucose, which releases ATP. In the Cori cycle, the liver converts lactate produced by muscle back to glucose for muscle fuel in an ATP-dependent manner. Similarly, alanine can be used by the liver and is a preferred precursor for hepatic gluconeogenesis as part of the glucose-alanine cycle (see Fig. 6-1). Alanine is provided by either muscle during protein turnover or amino acids in the diet.

Metabolism of nitrogen-containing compounds in the body, including amino acids, produces ammonia, which is converted to urea, a less toxic substance, by a series of reactions that comprise the urea cycle. The urea cycle generates urea from ammonia produced from amino acid oxidation, in which certain amino acids enter the urea cycle directly as intermediates, including arginine. Increased catabolism of protein and the release of amino acids for gluconeogenesis lead to excess nitrogen production, negative nitrogen balance, and increased excretion of urea by the kidneys (see Fig. 6-1). Liver failure can lead to hepatic encephalopathy because of the buildup of nitrogenous compounds, including ammonia; inborn errors of metabolism also give rise to disorders from dysfunction of the urea cycle.

Regulation of the Amino Acid Pool

Anabolic or catabolic hormonal signaling, various pathophysiologic mechanisms, type and availability of nutrients, and their routes of administration are all factors that regulate the pool of free amino acids. During enteral nutrition (EN), the portal venous system delivers ingested amino acids to the liver; 25% of these reach the general circulation to supply the plasma pool of amino acids, 55% are converted to urea, 6% are used for the synthesis of constitutive plasma proteins (e.g., albumin, prealbumin), and 14% become liver protein. In a severe hypermetabolic response to surgery or trauma, there is a significant increase in demand for amino acids and proteins. Similarly, increase in demand is noted during growth, physical activity, pregnancy, and lactation.

Glucose-Alanine and Glucose-Lactate Amino Acid Cycles

After severe injury or major surgery, the rates of glucose uptake, glycolysis, and oxidation of BCAAs in muscle are increased. Stimulated by glucagon, the liver transfers the amino group from alanine via the urea cycle to produce pyruvate.

Pyruvate enters the gluconeogenesis pathway via the mitochondrial enzyme pyruvate carboxylase. Glucose is then synthesized and released back to the circulation. Of the 20 amino acids, 18 are gluconeogenic, with alanine being the most frequent source. This amino acid pathway is referred to as the glucose-alanine cycle.

Lactate is a byproduct of the anaerobic metabolism of glucose. In physiologic states, it is produced by red blood cells (anaerobic cells) and skeletal muscle and taken up by the liver, where it is initially converted to pyruvate and subsequently to glucose via the gluconeogenic pathway. This is commonly known as the glucose-lactate, or Cori, cycle. The reactions that convert lactate back to glucose require a great deal of energy, which is supplied through lipolysis and β-oxidation of fat (see Fig. 6-1).

In the critically ill patient, lactate serves as a global marker of tissue hypoperfusion and insufficient oxygen delivery. However, there are additional mechanisms to explain lactate accumulation in these patients; elevations in plasma lactate levels in severely injured patients may in part be related to increases in glucose flux and may not totally be a reflection of a deficit in oxygen availability (Fig. 6-5).⁸

FIGURE 6-5 Oxidative decarboxylation of pyruvate is a pivotal step in the overall oxidative metabolism of carbohydrates and fats. Overwhelmingly high levels of glucose may lead to lactate production, even in the presence of oxygen.

(Adapted from Gore DC, Ferrando A, Barnett J, et al: Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients. J Trauma 49:673–677, 2000.)

Intestinal Health

After dietary ingestion, polysaccharides such as fiber and starch undergo bacterial fermentation in the colonic lumen. Bacterial fermentation is essential for two major reasons: (1) support of the normal flora of the gut lumen, which in turn prevents colonization and subsequent infection (e.g., Clostridium difficile); and (2) production of acetoacetate, propionate, and butyrate (a short-chain fatty acid). Butyrate appears to be the preferred fuel of colonic mucosa cells, followed by acetoacetate, glutamine, and finally glucose, and butyrate is therefore essential for mucosal integrity. With the advent and prolonged use of elemental diets for the purpose of achieving total absorption within the small intestine, adequate delivery of fiber to the colonic mucosa is not ensured, bacterial fermentation does not take place, butyrate-producing bacteria are suppressed, and mucosal integrity may be consequently impaired.

Following critical injury, there is thinning of the gut mucosa and a decrease in gut mucosal weight, protein, and DNA content, which are indicative of decreased cellular mass and absorptive surface of the small bowel, changes that result from an increased rate of small bowel mucosal apoptosis, with a relative decrease in small bowel cell proliferation.⁹ These changes have been associated with decreased absorption, deranged transportation, and increased gut permeability.

Protein Turnover

Protein turnover is continuously altered by dietary intake, synthesis, and protein breakdown. Amino acids are removed from the free pool of amino acids by protein synthesis and conversion to urea in a dynamic balance referred to as protein turnover. Net synthesis of protein is indicative of an anabolic state, whereas degradation of protein is indicative of a catabolic state. During critical illness, sepsis, trauma, or severe burn injury, there is an increased rate of synthesis and breakdown of muscle protein, although the magnitude of the latter is more significant and leads to a catabolic state.⁶ Increased proteolysis initiates an imbalance of the supply and demand of free amino acids; if protein breakdown persists, net protein catabolism leads to significant muscle wasting.

Proteolysis

The triggers and cellular signaling pathways that induce proteolysis and muscle catabolism, along with therapeutic targets and therapies to prevent muscle wasting, are areas of intense research interest but remain incompletely understood. Proteolysis may be induced to varying degrees by a range of conditions that include fasting, cancer, neurologic genetic disorders, disease, diabetes, sepsis, AIDS, burns, hyperthyroidism, and excess glucocorticoids. The terminal biochemical process involves conjugation of ubiquitin to the amino group of lysine residues in proteins through a series of enzyme: (1) E1 ubiquitin-activating enzyme; (2) E2 ubiquitin-conjugating enzyme; and (3) E3 ubiquitin ligases. The key enzymes in this process are the E3 ligases. Three E3 ubiquitin ligases are expressed in muscle: atrogin-1 (also known as MAFbx), muscle RING finger protein 1 (MuRF1), and E3α-I. Approximately 85 specialized proteases that act on ubiquitin are encoded in human genes. Nuclear factor-κB is a major transcription factor that triggers muscle protein degradation via ubiquitination.

Recent studies have proposed that Akt1 is the balancing force between muscle atrophy and hypertrophy. Insulin-like growth factor-1 (IGF-1) and other anabolic stimuli activate the PI3K-Akt1 pathway, leading to the activation of downstream targets (mTOR and S6K1) that stimulate muscle protein synthesis and hypertrophy (Fig. 6-6). Conversely, Akt1 is responsible for the phosphorylation status of the Foxo family of transcription factors. If Foxo is phosphorylated by Akt1, it leaves the nucleus and becomes inactive, thereby preventing the induction of atrophy. However, if Akt1 activity is suppressed, Foxo becomes dephosphorylated and transcriptionally active and directly binds the key atrogin-1 ubiquitination gene, among others, inducing increased protein degradation and muscle atrophy.

FIGURE 6-6 The proteins Akt1 and Foxo at the decision point of atrophy versus hypertrophy.

(From Hoffman EP, Nader GA: Balancing muscle hypertrophy and atrophy. Nat Med 10:584–585, 2004.)

Vitamins and Micronutrients

In addition to requiring macronutrients, proteins, carbohydrates, and fats, numerous cellular processes and enzymes require the provision of trace quantities of vitamins, minerals, and trace elements (Table 6-2).

Table 6-2 Vitamins and Micronutrients in Surgical Care

Decreased levels of vitamins and trace elements have been implicated in impaired wound healing and immune dysfunction. Micronutrients and vitamin deficiencies are rarely seen in patients receiving EN but can occur more often in patients receiving parenteral nutrition (PN). Although deficiencies are avoidable with adequate supplementation, some vitamins and micronutrients require portal passage for conversion or activation, which is potentially bypassed with parenteral infusion. In patients with short bowel syndrome or extensive ileal resection, vitamins and micronutrients that normally require enterohepatic circulation are not adequately absorbed or activated. Patients with adult-onset pernicious anemia or atrophic gastritis with hypochlorhydria can have vitamin B₁₂ deficiency. Fat malabsorption induced by pancreatic insufficiency can lead to inadequate uptake of fat-soluble micronutrients. Extensive inflammatory bowel disease can result in iron and vitamin deficiencies. Plasma levels of trace elements are also significantly depressed for prolonged periods after injury because of increased urinary excretion and significant cutaneous losses.

Nutritional Assessment and Monitoring

Nutritional assessment of surgical patients includes evaluation of preexisting malnutrition or obesity, medical conditions and metabolic disorders, malabsorption, dental disease, drug dependency, and alcoholism. In addition to requiring a comprehensive medical history and physical examination, nutritional assessment may include relevant laboratory tests, anthropometric measurements, and other assessments of body composition and energy expenditure, combined with the serial evaluation of results and response to therapy (Box 6-1). Malnutrition may exist primarily because of underlying pathology or inadequate intake, secondary to disease, trauma, and inflammatory processes or as a consequence of surgical interventions and operative procedures.

Stress responses to trauma and critical illness lead to derangement of normal metabolic and physiologic processes, induction of inflammatory cascades, hepatic acute-phase protein responses, capillary leakage of plasma proteins and subsequent fluid compartment shifts, elevated basal energy expenditure, and catabolism of muscle protein, which result in organ dysfunction and associated morbidity. The aim should be to assess and accurately meet nutritional demands while avoiding overfeeding.

Overfeeding is detrimental, leading to hypercapnia and metabolic acidosis, hyperglycemia, hypertriglyceridemia, hepatic dysfunction, and azotemia.¹⁰ Goal-directed nutritional support is essential for improving outcomes following trauma and surgery and should be based on repeated assessment of response to feeding. Nutritional support should be started as soon as possible if circumstances indicate that adequate oral intake will be unlikely for a patient within 5 days or if a preexisting nutritional deficit is present.

Malnutrition and Starvation

Up to 50% of patients admitted to the hospital may be malnourished ¹¹ and an additional 25% to 30% become malnourished during their hospital stay. Malnutrition can occur as a result of protein-calorie deficiency, predominant protein deficiency, and deficiency of specific micronutrients. Malnutrition can also result from a hypermetabolic state following trauma, critical illness, sepsis, severe burns, or major surgery. It leads to impairment of multiple organ systems, including the immune system, leading to an increased incidence of infection and delayed wound healing. Severe malnutrition and prolonged starvation eventually lead to reduced GI barrier function, respiratory insufficiency, skeletal muscle wasting, decreased myocardial mass, renal atrophy, diastolic cardiac dysfunction, and decreased sensitivity to inotropic agents.

In the metabolic response to starvation, glycogen serves as the primary body fuel for the first 12 to 24 hours. Once glycogen stores are depleted, gluconeogenesis increases and amino acids begin to be degraded to fuel. Over time, ketone bodies from fat can serve as the primary oxidative fuel source. In hypercatabolic states, increases occur in catabolic hormones—cortisol, glucagon, catecholamines, and a number of inflammatory mediators. Hyperglycemia, elevated lactate levels, and increased urinary nitrogen excretion are characteristic features. The body uses fat and muscle as sources of energy. Muscle protein is used preferentially relative to visceral protein. Hence, the rate of loss of lean body mass exceeds that of overall weight loss.

Malnutrition caused by starvation responds to restoration of nutrition, whereas malnutrition secondary to the stress response and disease is often less responsive to nutritional support. Enteral feeding enhances the immune response, and increasing the protein content of the enteral diet has been shown to reduce immunosuppression.

Physical Body Measurements

Evaluating Caloric Requirements

Determining nutritional requirements of critically ill patients is essential because the provision of inadequate or excess calories can adversely affect outcome. Measuring the resting energy expenditure (REE) or basal metabolic rate can be extremely useful in the nutritional management of surgical patients under various types of stress who may experience significantly increased energy demands, which can be difficult to predict. Estimates of caloric requirements can be made using several different equations, calculated using blood gas measurements with the Fick equation, or measured by indirect calorimetry using bedside metabolic carts to determine REE.

Energy Expenditure Equations

Several different equations are commonly used to estimate nutritional requirements. These formulas provide only an estimate because energy demands may vary considerably among patients and requirements will also depend on a patient’s condition and activity level. These formulas are based on parameters including age, gender, height, and weight. Examples include the Harris-Benedict,⁶¹ American College of Chest Physicians, Ireton-Jones (1997), Penn State (2003), and Swinamer (1990) equations. In severely burned patients, these and other equations can estimate nutritional requirements. Included in these other equations are the Curreri and Galveston formulas, which additionally take into consideration body surface area and burn percentage. It is important to select the appropriate equation based on age and correct estimate of degree of injury, because their inappropriate use can lead to significant overestimation of caloric needs and increased risk of overfeeding.

Harris-Benedict Equation

Most patients can be fed adequately by supplying 100% to 120% of the predicted REE as calculated by the Harris-Benedict equation.¹⁴ This equation estimates basal metabolic rate (BMR), assuming a normal resting physiologic state.

For men:

For women:

Therefore, multiplication by a stress factor is generally needed, usually ranging from 1.2 to 1.5 in ventilated patients with sepsis. A stress factor of 1.1 and 1.2 has been suggested for minor and major elective surgery, 1.35 and 1.6 for skeletal trauma and head injury, and 1.1, 1.5, and 1.8 for mild, moderate, and severe infection, respectively, has also been suggested.¹⁵ This may rise to 1.2 to 1.95 in burn injuries of 40% to 100% of total body surface area (TBSA).

Indirect Calorimetry

An evaluation of the metabolic status can be performed by indirect calorimetry using bedside metabolic carts, which measure REE using expired gas volumes; VO₂ and carbon dioxide production (VCO₂) are measured directly. A tight-fitting face mask or connection to a mechanical ventilator circuit is needed. The measured REE value may need to be increased approximately 10% to 20% if used to estimate caloric requirements in patients to allow for activity and fluctuations in their overall metabolic rate.

Measurements obtained are generally reliable and reproducible over a wide range of catabolic conditions, metabolic rates, and values of FIO₂.Indirect calorimetry may also be used to monitor the adequacy of feeding by calculating the respiratory quotient (RQ = VCO₂/ VO₂) and evaluating substrate uptake. An RQ in the range of 0.7 to 1.0 is seen in the normal uptake of mixed substrates. An RQ of 0.7 or less is consistent with pure fat uptake and is indicative of underfeeding, whereas an RQ higher than 1.0 may indicate fat synthesis from carbohydrate and overfeeding. Overfeeding has been shown to be detrimental to critically ill patients and induces a rise in VCO₂ because of increased lipogenesis.¹⁶ Such a rise in VCO₂ may also contribute to difficult weaning from ventilatory support.

Poor agreement between measured and predicted REEs has been reported in certain circumstances, being as high as 635 ± 526 kcal/day in severely burned children.¹⁷ Bedside carts are therefore recommended to calculate optimal nutritional requirements in certain patient populations, including the following: (1) severely burned children; (2) ventilator-dependent patients; (3) patients with clinical signs of overfeeding or underfeeding; (4) patients with spinal cord injury or coma; (5) critically ill patients who are morbidly obese; and (6) those with failure to respond adequately to the use of diets determined according to equations, with failure determined by lack of improvement in clinical or biochemical nutritional measurements.

Dual-Energy X-Ray Absorptiometry

Dual-energy x-ray absorptiometry is a useful technique for monitoring long-term nutritional progress. It is used to measure body composition changes, including lean body mass, fat mass, and bone density. It is a noninvasive investigation, with scans obtained with the patient lying supine on a table. It measures the attenuation of two x-ray beams, one high energy and the other low energy, and it delivers a low dose of radiation. These measurements are compared with standard models used for bone and soft tissue. Results are separated into lean body mass, fat mass, and bone mineral content. Maintaining and enhancing skeletal muscle as lean body mass is a principal objective of nutritional support; these measurements are therefore useful in nutritional assessment. Assessment of body composition when patients have been treated with surgical staples or are undergoing fluid shifts in cellular and whole-body water may confound the assessment of lean body mass.

Monitoring Nutritional Status

Careful monitoring is necessary to ensure optimal feeding and prevent underfeeding or overfeeding, regardless of the method used to estimate nutritional needs. This involves regular clinical assessment of vital signs, respiratory status, functional improvement, and wound healing, all of which may present important clues about the true nutritional status. In addition to clinical assessment, monitoring trends in a range of parameters will serve to guide nutritional support and the need to enhance or adjust feeding regimens.

Nitrogen Balance

Nitrogen balance can be calculated to monitor the adequacy of protein intake. A negative nitrogen balance occurs when the excretion of nitrogen exceeds the daily intake, an indication of muscle breakdown, whereas a positive nitrogen balance is associated with muscle gain.

Nitrogen balance can be estimated using equations based on common measurements, such as urine urea nitrogen (UUN), urine nonurea nitrogen (estimated as 20% of UUN), 24-hour urine output (UO), and an additional 2 g/day to account for nonurinary nitrogen losses (stool and skin).

Serial monitoring of total nitrogen balance in patients permits one to evaluate the response to nutritional support and identify patients at risk of developing muscle protein loss. Persistent loss of nitrogen and protein catabolism leads to decreased muscle strength, altered body composition, increased infectious complications, and subsequent delayed rehabilitation.

Pediatric Assessment

Nutritional assessment in children, in addition to clinical history, physical examination, and biochemical markers, also includes plotting their growth on percentile charts. The Centers for Disease Control and Prevention (CDC) has published revised, standard, gender-specific percentile charts for growth, including stature and weight for age and BMI. These charts are demographically representative of the U.S. population from 2 to 20 years, with charts also available for younger children (Fig. 6-7). These charts are used to monitor a patient’s long-term nutritional progress. A patient’s position on the growth chart is the best simple tool to evaluate overall nutritional status in the acute setting. A value below the fifth percentile or a trend line crossing two major percentile lines indicates a serious failure to thrive.

FIGURE 6-7 Stature- and weight-for-age percentile charts for boys ages 2 to 20 years.

(From Centers for Disease Control and Prevention: Growth charts, 2000, http://www.cdc.gov/growthcharts.)

Serum Proteins

A range of serum proteins are commonly used as indicators of nutritional status, with albumin being the most frequently used. Albumin accounts for more than 50% of the total protein in serum and is the major contributor to colloid osmotic pressure. An albumin level below 3 g/dL suggests suboptimal nutrition and has been used as the primary preoperative serum marker of malnutrition (Table 6-3). Albumin has a long half-life (t_1/2), approximately 20 days, and perioperative albumin levels have been found to be a better prognostic indicator than anthropomorphic measurements for morbidity and mortality in surgical patients.^18,¹⁹ Serum proteins with a shorter circulating duration are also used; these include transferrin (t_1/2 = 10 days), prealbumin (t_1/2 = 3 days), and retinol binding protein (t_1/2 = 12 to 24 hours), because these are more sensitive indicators of recent changes.

Table 6-3 Surgical Risk by Serum Albumin Level

SERUM ALBUMIN (g/dL)	30-DAY MORTALITY RATE (%)	30-DAY MORBIDITY RATE (%)
>4.5	≤1	≤10
3.5	5	25
3.0	9	35
2.5	15	45
<2.1	≈30	65

Perioperative levels of serum albumin have been shown to be powerful predictors of morbidity and mortality.

Adapted from Gibbs J, Cull W, Henderson W, et al: Preoperative serum albumin level as a predictor of operative mortality and morbidity: Results from the National VA Surgical Risk Study. Arch Surg 134:36–42, 1999.

During the acute stress response to injury, significant downregulation of 50% to 70% of proteins with a longer half-life, such as albumin and transferrin, occurs in parallel to the upregulation of hepatic acute-phase proteins. The degree of downregulation of constitutive proteins after trauma is used as a predictor of mortality and stress severity. Patients with albumin levels below 3 g/dL show an independently associated increased risk of developing serious complications within 30 days of surgery, including sepsis, acute renal failure, coma, failure to wean from ventilation, cardiac arrest, pneumonia, and wound infection.

Albumin levels are also useful in detecting protein-energy malnutrition, which is frequently difficult to recognize in patients not presenting with low body weight and results from increased demands associated with the stress of illness, injury, or infection. If these requirements are not met from dietary sources, body protein stores are depleted, leading to complications (e.g., malabsorption, impaired immunologic response, reduced production of other constitutive proteins). Counterintuitively, IV administration of albumin is usually ineffective because it degrades quickly after infusion and does not treat the underlying cause of malnutrition.

The use of serum protein levels as indicators of nutritional status may be limited in the acute phase following injury, inflammation, infection, and surgical stress. Fluid shifts and increased capillary permeability lead to protein leakage from the intravascular compartment, which results in hemodilution and false hypoproteinemia.

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Aug 1, 2016 | Posted by admin in CARDIAC SURGERY | Comments Off

Thoracic Key

Fastest Thoracic Insight Engine

Metabolism in Surgical Patients

Nutritional Requirements

Carbohydrate Metabolism

Lipid Metabolism

Protein Metabolism

Regulation of the Amino Acid Pool

Glucose-Alanine and Glucose-Lactate Amino Acid Cycles

Intestinal Health

Protein Turnover

Proteolysis

Vitamins and Micronutrients

Nutritional Assessment and Monitoring

Malnutrition and Starvation

Physical Body Measurements

Body Weight

Anthropometric Measurements

Ideal Body Weight

Body Mass Index

Interpretation of Body Mass Index

Evaluating Caloric Requirements

Energy Expenditure Equations

Harris-Benedict Equation

Indirect Calorimetry

Dual-Energy X-Ray Absorptiometry

Monitoring Nutritional Status

Nitrogen Balance

Pediatric Assessment

Serum Proteins

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Metabolism in Surgical Patients

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