following invasive infection, in a pattern that is similar to that described for injury. Visceral amino acid

uptake is accelerated during sepsis, and this is matched by faster amino acid efflux from skeletal muscle.

In infected burn patients, splanchnic amino acid uptake is amplified over 50% above rates in uninfected

burn victims with comparable injuries. These amino acids serve either as glucose precursors, or building

blocks for acute-phase protein synthesis.

Fat is another major fuel utilized for energy in infected patients. Increased fat catabolism is

particularly profound in patients during periods of inadequate nutritional support or relative starvation.

Lipolysis is accelerated among other reasons by a heightened sympathetic activity, and serum

triglyceride levels reflect the balance between synthesis in the liver and storage in the peripheral

adipose tissue. Marked hypertriglyceridemia has been associated with certain gram-negative infections,

but frequently triglyceride concentrations are normal or low, indicating enhanced utilization and

clearance by other organs. Infected patients cannot convert fatty acids to ketones as efficiently in the

liver, and do not adapt to starvation as well as their fasted, unstressed counterparts. It is postulated that

the low ketone state of infection is a consequence of the hyperinsulinemia, which in turn follows insulin

resistance in high-degree catabolic states.

Trace elements and electrolytes (zinc, iron, potassium, magnesium, and inorganic phosphate)

typically follow alterations in nitrogen balance. Although the iron-binding capacity of transferrin

typically remains unchanged in early infection, free iron cannot be found in the plasma of patients with

severe pyrogenic infections. Similar changes are seen in zinc levels. These decreases cannot be totally

accounted for by total body losses, rather an accumulation of these elements appears to occur in the

liver, through not yet elucidated mechanisms. Unlike iron and zinc, serum copper levels generally rise,

seemingly due to greater ceruloplasmin synthesis in the liver.

Metabolic Response to Cancer and Acquired Immunodeficiency Syndrome

Patients with cancer and acquired immunodeficiency syndrome (AIDS) have similar metabolic states,

characterized by chronic malnutrition, typically a result of anorexia and treatment side effects, and

prolonged low-grade inflammatory changes. Cancers of the aerodigestive tract interfere with taste,

swallowing and/or digestion, precluding adequate caloric and/or protein intake. Supplementation with

zinc and B vitamins may help taste-related symptoms, and soft mechanical diets may allow greater

caloric intake in patients with swallowing difficulties or proximal gastrointestinal tract malignancies.

The aggressive management of nausea and vomiting, may also afford greater interest in food.

Cancer- and AIDS-related cachexia is seen in the later stages of disseminated disease and represents a

chronic catabolic state due to unrelenting inflammation that is difficult to reverse, even with adequate

caloric and protein supplementation. Proinflammatory cytokines (TNF, IL-1, and IL-6) are constantly

released in response to the tumor or an infectious source in AIDS, respectively, and lead to a chronic

state of muscle wasting and fat loss. The cachexia of cancer and AIDS is difficult to manage, as

removing the inflammatory stimulus can prove elusive. However, mitigation of the chronic, low-grade

inflammatory response may be useful, and so can aggressive nutritional supplementation and appetite

stimulants.40

Another practice that is becoming increasingly popular is the repurposing of the dietary balance of n-6

to n-3 fatty acids. Thirty eight fatty acids from the diet eventually become incorporated into cells’

plasma membranes, influencing their function and characteristics, and act as precursors for eicosanoid

synthesis.39 The eicosanoids produced depend on the type of fatty acids found in plasma membranes.

The n-6 fatty acid linoleic acid is converted to arachidonic acid, which in turn gives rise to

proinflammatory eicosanoids PG2 and LT4. The n-3 fatty acid linolenic, eicosapentaenoic, and

docosahexaenoic acids yield more anti-inflammatory PG3 and LT5. These eicosanoids interrupt the

release of IL-6, thus potentially allowing IGF-1 levels to normalize in cachectic patients.40 While a

typical Western diet is high in n-6 to n-3 fatty acids ratio (∼15:1), more therapeutic ratios of 2:1 to 4:1

can be targeted, in addition to maximizing protein and caloric intake. Such efforts have been met with

improving clinical outcomes in patients with pancreatic cancer41 or generalized malignancies.42

Stimulants of the Stress Response

Hypovolemia and End-Organ Hypoperfusion

Following hemorrhage, pressure receptors in the aortic arch and carotid, and volume (stretch) receptors

in the left atrial wall detect the acute drop in circulating blood volume and pressure and respond by

signaling the central nervous system. Activation of the sympathoadrenergic axis leads to a rise in stroke

volume to maintain a perfusing pressure, at the expense of tachycardia. ADH and aldosterone are also

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released, in an attempt to restore circulating plasma volume. ADH is released by the posterior pituitary

in response to hypotonicity and increases water reabsorption in the renal tubular apparatus. Aldosterone

is produced through activation of the renin–angiotensin system, when the renal juxtaglomerular

apparatus senses a drop in the renal perfusion pressure, and also increases reabsorption of sodium and

water. These mechanisms are only partly effective and, if bleeding is not controlled surgically and

resuscitation inadequate, peripheral tissue oxygenation does not suffice to meet metabolic demands and

metabolism switches to anaerobic metabolism, leading to lactate production and lactic acidosis.

Tissue Damage

Tissue damage appears to be one of the principal factors that can set the stress response into motion.

Hypovolemia itself is rarely an adequate stimulus to trigger a hypermetabolic response, unless

associated with extensive tissue damage or infection. However, if hypoperfusion is prolonged, cellular

death may ensue, which in turn will lead to release of toxic products that can initiate the “stress”

response.

Pain

Pain can be an important activator of the sympathoadrenergic response and lead to a catecholamine

surge with the metabolic effects described earlier. Local tissue destruction is sensed as pain centrally,

which triggers numerous efferent pathways preparing the body for what is termed the “fight or flight”

response.

Determinants of the Host Response to Stress

Each individual, depending on their genetic traits and certain environmental parameters may respond

differently to similar tissue injury patterns. The idiosyncratic nature, intensity, and duration of the

stress response may vary extensively in numerous ways in individuals with certain similar genetic and

body composition characteristics.

Body Composition

Body composition is a major determinant of the metabolic response seen in the acute phase after

surgical or accidental trauma. Posttraumatic nitrogen excretion is directly proportional to the size of the

lean body mass. The balance between nitrogen intake and output is a useful marker of protein

metabolism. A greater muscle mass due to greater long-term physical activity may also confer an

advantage during acute surgical illness and starvation, as the ability of the lean body mass to provide

amino acids for gluconeogenesis during acute illness when it is needed the most, is optimal. Conversely,

excessive adiposity may affect outcomes after intense stress, and this is likely due to an abundance of

proinflammatory precursors.43

Baseline Nutritional Status

A strong relationship exists between preoperative protein depletion and postoperative complications.4

Protein-depleted patients have lower pulmonary muscle strength and reserve, and are more susceptible

to infectious complications, including of the respiratory tract, as well as of the surgical site. Patients

with poorer baseline nutrition also experience impaired wound healing and are subject to longer

postoperative hospital stays.

Age and Gender

Certain patterns in the metabolic response to surgical pathology that occur with aging can be attributed

to alterations in body composition. Although weight remains roughly stable, fat mass tends to increase

with age, while lean body mass tends to decline. The loss of strength that accompanies immobility,

starvation, and acute surgical illness may have significant consequences. Although the increased energy

requirements after elective surgery occur essentially independent of age, the capacity of muscle to serve

as a source of amino acids may be limited during acute surgical illness in the elderly, and muscle

strength may rapidly become inadequate for respiratory function.

In addition to a smaller muscle mass, older age is commonly associated with a greater prevalence of

cardiovascular and pulmonary disease. Relatively decreased arterial compliance, lower baroreceptor

sensitivity, and a blunted response to the catecholamine surge may impair the cardiovascular

homeostatic response during acute surgical illness. Thus, tissue oxygenation may not be able to meet the

heightened demand.

Gender, in addition to age, may affect the body’s ability to adapt to surgical stress. Observed

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differences in the metabolic response between men and women in general reflect differences in body

composition. Lean body mass, as a proportion of total body weight, is lower in women than in men.

This difference is thought to account for the lower net loss of nitrogen after major elective abdominal

surgery in women. Women in general, have approximately half the skeletal muscle mass of men of the

same age. Therefore, young muscular men experience the greatest nitrogen losses during acute surgical

illness, as opposed to elderly, sedentary women.8

NUTRITIONAL SUPPORT

Nutritional Support in Elective Surgery

Most patients undergoing elective operations are adequately nourished, and are typically only fasted the

evening before surgery. Unless the patient has suffered significant preoperative malnutrition (subjective

global assessment class C) or has a major intraoperative or postoperative complication, intravenous

solutions containing 5% dextrose may be administered for up to 5 to 7 days with no detrimental effect

on clinical outcomes. In patients who present with the evidence of starvation-related malnutrition,

preoperative addition of balanced macronutrient, and high-protein supplementation could be useful.

This preoperative support should be initiated as far in advance as possible, even though it is estimated

that the minimum time required to derive any benefit from this support is in the range of 2 to 4

weeks.44 During this period, electrolyte abnormalities should be addressed, and early involvement of a

nutritionist would be advisable.

Bowel function typically returns within the first 5 to 7 postoperative days in the majority of surgical

patients, and an oral diet or enteral feedings can be resumed. The increased cost of feedings and the

potential complications associated with parenteral nutrition cannot be justified. Conversely, in patients

who are malnourished preoperatively or prolonged postoperative ileus has rendered them unable to be

fed enterally for more than 5 to 7 days, nutritional support should be considered. The nutritional status

should be assessed early, so this piece of information can be integrated into decision-making and

nutrition care planning. Enteral feedings are superior and always preferred to parenteral nutrition in

patients who can tolerate an enteral diet. Standard high-protein feeding formulas are adequate. The

choice of product and volume of feeding are based on the results of the nutrition assessment. The

majority of tube feeding formulas today are rich in water-soluble dietary fiber, which is considered

standard in the nutritional care of the surgical patient. Specific adjustments can be undertaken, if special

considerations (e.g., cardiac failure, renal failure, diabetes, etc.) have to be made. Preoperative addition

of a balanced macronutrient high-protein supplement is useful to initiate as far in advance of surgery as

possible, although in this severely malnourished population, the time needed to see benefit from

supplementation is unknown (estimated minimum of 2 to 4 weeks).

6 One of the best studies to date evaluating the efficacy of preoperative TPN was published by the

Veterans Affairs Total Parenteral Nutrition Cooperative Study Group.4 Over 3,000 patients requiring

mostly elective gastrointestinal procedures were randomized to receive parenteral nutritional support

for at least 7 days preoperatively versus none, if they were deemed to be malnourished preoperatively.

Patients with severe malnutrition (>15% weight loss and serum albumin <2.9 mg/dL) preoperatively

had fewer noninfectious complications (impaired wound healing), if they were provided TPN before

surgery, however, infectious complications (pneumonia, surgical site infections, and line infections)

were more common in the TPN group. This study strongly suggests that preoperative TPN should be

considered only to severely malnourished patients who cannot be fed via the enteral route.

Numerous studies that have followed have reached similar conclusions, and have led the SCCM and

ASPEN to recommend targeted preoperative nutritional support for those deemed malnourished. This

support should ideally be oral, enteral, or in rare circumstances parenteral and with therapeutic intent.6

In fact, while initial guidelines advocated the use of artificial nutrition if preoperative weight loss

>10% has occurred or oral intake is not deemed achievable for more than 7 days postoperatively,

interest in supporting all surgical patients perioperatively has been on the rise, regardless of baseline

nutritional status.45

Nutritional Support in Critical Care

7 While resuscitation, bleeding control and preservation of the vital body functions, such as

maintenance of gas exchange and supporting of adequate cardiac output, remain immediate priorities

for survival in any critically ill surgical patient, it is increasingly recognized that nutritional support is

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