an integral part of the metabolic care of the critically ill, and aggressive pursuit of target energy

requirements is associated with optimal wound healing, recovery, and rehabilitation. Critically ill

patients commonly have anorexia that can be adaptive or maladaptive and may be unable to be fed by

mouth volitionally for periods, which can range from days to months, and severe malnutrition can

complicate their course and adversely affect outcomes, unless they are provided with enteral or

parenteral nutrition.46 Several studies have underlined the association between energy deficit in critical

illness and longer ICU stays, greater incidence of infectious complications, and even mortality.47–50 The

finding that enteral nutrients exert a trophic effect on the cellular integrity and function of the gut

mucosa has provided the rationale for initiating enteral feedings early in the course of critical illness. In

fact, evidence from observational studies appears to support that critically ill patients who were fed

earlier had better overall outcomes compared to those that did not,51 and these improved outcomes

have led critical care nutrition to be at the forefront of ongoing research worldwide. Therefore,

regardless of baseline nutritional status, any critically ill patient who is not expected to resume an oral

diet within 3 to 4 days should have nutritional support instituted as soon as technically and logistically

feasible, ideally within 24 to 48 hours after admission, and have their blood glucose levels maintained

<140 mg/dL.52 Patients on enteral nutrition, should have their head of bed elevated at 45 degrees, or

be in steep reverse Trendelenburg position if spinal precautions preclude this measure, to minimize

aspiration risk.18,20

The optimal method of estimating daily energy requirements in the critically ill remains a subject of

debate. It would be ideal if energy requirements were calculated precisely on a daily basis using indirect

calorimetry, as this method appears to lead to greater energy provision than less precisely calculated

energy targets, even though this practice was associated with a greater incidence of infectious

complications and a longer overall ICU length of stay.53 Indirect calorimetry, however precise, can be

impractical, if not even impossible to apply in certain critically ill individuals.54 Additional challenges

facing critical care nutrition include the frequent interruptions in nutrition delivery for a variety of

reasons, including delayed gastric emptying and transfers outside the ICU for diagnostic or therapeutic

procedures. When protocols to aggressively advance nutrition are in place, it appears that critically ill

patients are able to achieve their caloric goals earlier, even though these practices may not necessarily

translate to better overall outcomes.55–57 With regard to delayed gastric emptying, which is commonly

cited as a reason for slow advancement of enteral feedings, it appears that advancing tube feedings

without measuring or accepting residual volumes as high as 500 cc/4 hours results in quicker attainment

of the caloric goals, with no concomitant rise in the incidence of nutrition-related adverse events.58 The

use of prokinetic agents (erythromycin may be more effective than metoclopramide), as well as

postpyloric feeding delivery has also been advocated to minimize the issue of delayed gastric emptying,

however, other than achievement of nutritional goals being slightly earlier in the course of critical

illness, no definitive improvement in outcomes has been demonstrated.59–62 There is some divergence

on whether immune- or inflammation-modulating feeding formulas are indicated in some critically ill

patients. There is at least one quality study that has been published since the guidelines that support the

use of such feedings in patients with sepsis and risk for acute respiratory distress syndrome or acute

lung injury.63

Access Routes for Nutrition

Enteral or Parenteral

8 An issue with reliance solely on enteral nutrition is that attaining caloric targets may prove elusive,

due to a partly functional gastrointestinal tract or side effects associated with enteral feedings. While

enteral feedings are always preferable to parenteral nutrition in general, the timing of initiation of TPN

in patients unable to tolerate or with contraindications for enteral feedings remains controversial.

European guidelines recommend early initiation of TPN to minimize nutritional deficits, while North

American guidelines favor hypocaloric enteral nutrition for up to 1 week in patients with good

nutritional baseline before considering TPN.48,49 The rationale on the delay in TPN administration is

based on complications associated with the use of TPN, such as infections, hyperglycemia,

hypertriglyceridemia, and liver function abnormalities.64–67 The latter seems to be supported by more

recent high-quality data that demonstrate that patients receiving partial enteral nutrition demonstrate a

lower incidence of ICU-acquired weakness, spend less time in the ICU and the hospital, and require

shorter length of vital-organ support, and incur less costs, compared to their counterparts in whom

partial enteral nutrition was supplemented with TPN.68–71 However, conflicting data exist on the effect

of nutritional supplementation with TPN on infectious outcomes in patients receiving hypocaloric

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enteral feedings from more recent trials.68,69,72 In critically ill patients with a relative contraindication

(e.g., gastric residual volumes >500 mL or postoperative ileus) for early enteral nutrition, it appears

that early TPN helps decrease total length of stay on mechanical ventilation.73 Whether early parenteral

nutrition is beneficial in patients with an absolute or prolonged contraindication for enterally

administered nutrition remains a topic of debate, even though it is fairly well established that the

greater incidence of infectious complications may outweigh the benefits of early achievement of

nutritional goals in patients in their first 5 to 7 days in the ICU.68,74

Total Parenteral Nutrition Considerations

As the term implies, and due to the high osmolarity of its content, TPN must be delivered centrally to

minimize the risk of venous sclerosis. Patients on TPN therapy should be monitored regularly by

measuring blood sugar, serum electrolytes, and liver function tests, as abnormalities in these

laboratories are common. TPN-related complications can be broadly categorized into those that are

access related, metabolic, and infectious. A list of these is summarized on Table 3-8.

Table 3-8 TPN-Related Complications

9 Hyperglycemia is common in surgical patients, especially during high-stress periods, or they were

relatively glucose intolerant or frankly diabetic at baseline. This side effect of TPN can generally be

controlled with subcutaneous or intravenous insulin administration if mild or moderate–severe

respectively, and eventually by adding insulin to the TPN formulation, once the daily insulin

requirements have been calculated. It has been shown that stressed individuals can maximally oxidize

up to 4 to 5 mg of glucose/kg/min. For a 70-kg man, this is equal to approximately 400 to 500 g/day

(1,600 to 2,000 kcal/day). Therefore it is common for patients to receive up to two-thirds of their daily

caloric needs in carbohydrate form through TPN. Excess glucose can result in hyperglycemia and

glycosuria, can be converted to fat, and deposited in the liver. Glycosuria with its osmotic load can lead

to osmotic diuresis, which can be misinterpreted as a sign of adequate resuscitation status or transition

to recovery phase, while the patient may actually be clinically worsening.

Fat is an important fuel for the critically ill, as stressed patients preferentially utilize endogenous fat

as an energy source. Fat oxidation is only minimally affected by carbohydrate administration during

stress, unlike traditional starvation, and glucose infusion above certain levels may lead to hepatic

steatosis. Lipids are commonly added to TPN formulations to help meet the caloric requirements, as

well as to provide the essential fatty acids and to minimize complications associated with the infusion of

large amounts of carbohydrate-containing fluids. Lipid emulsions for TPN solutions are mostly vegetable

fat based, and contain primarily long-chain fatty acids. Inclusion of lipids in the TPN provides the

essential linoleic acid, inhibits lipogenesis from carbohydrates, and helps lower the respiratory quotient

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(RQ), which may benefit patients with carbon dioxide retention. However, formulations with a high n-6

polyunsaturated fatty acid content (linoleic acid in particular) may attenuate acute lung injury,75 and by

affecting plasma membrane fluidity, the ability to phagocytose bacteria may be impaired. Newer

nutritional methods of modifying the catabolic response to injury and infection propose the use of n-3

fatty acids, which may decrease eicosanoid synthesis and thereby diminishing the vasoconstriction,

platelet aggregation, and immunosuppression that may occur when n-6 derivatives are given. Studies

suggest that n-3 fatty acids may be of benefit to the critically ill patient.76

The amounts of the various electrolytes provided to patients receiving TPN vary, depending on

previous volume status and preexisting electrolyte abnormalities. Careful monitoring of serum

electrolyte levels is critical, especially during the acute phase of disease or in severely malnourished

individuals, because as metabolism switches to the anabolic phase, potassium and phosphate can move

rapidly into the intracellular compartment, leading to potentially fatal hypokalemia or

hypophosphatemia, in what is known as the refeeding syndrome.77 Vitamin and trace mineral levels,

although not as life-threatening, should also be occasionally monitored. The composition of a standard

TPN solution is shown in Table 3-9.

A significant downside of TPN is that the gastrointestinal tract goes into misuse, and evidence

suggests that this may exacerbate intestinal microflora translocation from the gut lumen to the

mesenteric lymph circulation, worsening total bacterial load and stress during an already compounded

clinical situation. Clinical evidence suggests that TPN, under certain circumstances, may accentuate

stress, and predispose to gut-derived infectious complications, and even multiple organ failure,78,79

while compared to enteral nutrition, it may minimize episodes of hypoglycemia and vomiting.80

Enteral Nutrition Considerations

10 11Enteral nutrition is safer and less expensive than parenteral nutrition, and numerous studies have

demonstrated the superiority of enteral nutrition compared to parenteral, in decreasing postoperative

infectious complications and increasing collagen deposition at anastomotic sites, improving wound

tensile strength.81 The gastrointestinal tract can be used for administration of complex nutrients that

cannot be provided as readily intravenously, such as polypeptides and fiber. Gut processing of many of

these nutrients stimulates hepatic protein synthesis, while intravenous administration bypasses the

portal circulation altogether. In addition to the systemic benefits of enteral nutrition, enteral feedings

afford significant local benefits on the gut mucosa itself. Enterocytes are being fed directly, and the

absorptive surface of the mucosa is stimulated and maintained. Luminal nutrients, such as glutamine and

short-chain fatty acids, are used as fuel by small bowel enterocytes and colonocytes respectively.82 The

trophic effects of luminal nutrition are well documented, even if small amounts of enteral feedings are

provided, and a growing body of evidence suggests that earlier enteral nutrition is preferable.83–85 An

additional immunologic benefit of enteral nutrition is that complex polypeptides and long-chain fatty

acids stimulate the production of gut-derived immunoglobulin A, which is important in reducing

bacterial translocation. Luminal nutrients also help maintain a normal pH and flora, thus diminishing

the risk of opportunistic bacterial overgrowth in the bowel. In addition to the physiologic, metabolic,

and immunologic benefits of enteral nutrition, safety and cost benefits also exist. Enteral feedings are

considered safer than parenteral nutrition. The latter places patients at a greater risk for hyperglycemic

events, which may partly inhibit neutrophil-mediated immune function, and may be the reason why

TPN-nourished patients may be at a greater risk for infectious complications, even though this risk may

be eliminated with tight glucose control.80 Finally, there are obvious cost benefits, as tube feedings are

in general cheaper than parenteral nutrition formulations.

Table 3-9 Composition of a Standard Total Parenteral Nutrition Formulation

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Although enteral nutrition is the preferred method for nutritional support in malnourished patients, or

subjects at risk for developing malnutrition and have an intact gastrointestinal tract, a problem surgical

patients are commonly facing is intestinal inactivity, especially after gastrointestinal procedures.

Postoperative ileus is frequent, reflects functional immobility of the gastrointestinal tract, and is

typically proportional to the amount of manipulation the bowel sustained during the surgical

intervention. Patients who are either unable to meet their daily caloric and nutrient needs are

candidates for enteral support. Factors that can help determine the timing of initiation of enteral

nutrition include preexisting malnutrition, current illness acuity and duration, estimated catabolic

activity, and anticipated return to per os intake. Contraindications to enteral feedings are usually

relative or temporary, and include short, obstructed, or perforated bowel, a gastrointestinal tract in

discontinuity, protracted vomiting, fistulas, or active gastrointestinal ischemia. While gastrointestinal

bleeding or worsening hemodynamic instability has been traditionally quoted as additional

contraindications, it appears that enteral nutrition can be safely administered during these.86–88

Despite the numerous benefits of enteral nutrition, it is not completely free of complications. These

can be categorized in access related, functional, and metabolic, and are summarized in Table 3-10. In

general, these can be avoided with meticulous care while inserting and maintaining feeding tubes,

considering using nasal bridles,89 ensuring head of bed elevation to minimize risk of aspiration, using

motility agents when gastric motility is suboptimal, closely monitoring patients’ metabolic profile and

adjusting content, or adding bulking agents if osmotic diarrhea develops.

Enteral feedings are generally categorized into intact or polymeric (protein, carbohydrate, and lipid

molecules exist in an unaltered form – usually given to patients without absorption or digestion

difficulties), hydrolyzed or monomeric (contain predigested proteins, simple sugars, and medium-chain

triglycerides – are a good option for patients with impaired digestive capacity), and modular (typically

contain one type of fuel, carbohydrate, lipids or fat, and can be combined to address each patient’s

specific needs). Some of the most commonly used enteric feeding formulas and their metabolic

characteristics are shown on Table 3-11.

Table 3-10 Enteral Nutrition-Related Complications

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Table 3-11 Commonly Used Enteral Nutrition Formulations

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Macro- and Micronutrient Selection

An additional topic of debate is whether selection of specific macro- and micronutrients to be included

in nutritional formulas, be it enteral or parenteral, can afford specific benefits to patients receiving

them, depending on the underlying pathology. Gluconeogenesis from amino acids (glutamine and

alanine) released from muscle protein breakdown cannot be fully suppressed with exogenous glucose

and insulin administration, due to the complex hormonal stress response the human body elicits during

critical illness, which results in relative insulin resistance. It was postulated, therefore, that exogenous

amino acid and oligopeptide infusion would help minimize lean body mass erosion. However, even

though the total nitrogen equilibrium appears to be shifted toward a more positive balance when this

practice is employed, it does not translate to better outcomes.90 Therefore, the optimal protein to total

energy ratio in critical illness remains largely unknown.

12 Glutamine is the most abundant nonessential amino acid and in humans it is predominantly

released with skeletal muscle proteolysis. It is one of the key precursors for hepatic gluconeogenesis at

times of stress, and low glutamine levels have been associated with poor outcomes in critical illness, as

it is an important nutrient necessary for the function of immune cells, enterocytes, and hepatocytes. It

has been postulated that low glutamine levels are a consequence of muscle wasting, and a meta-analysis

of early randomized controlled trials suggested that glutamine supplementation may help decrease

infectious complications, hospital length of stay, and even mortality.91 However, this finding has not

been replicated in newer, higher-quality studies, and in fact, it appears that aggressive glutamine

supplementation may increase risk of death in patients with organ failure.92–94 These findings do not

support glutamine supplementation routinely. Its supplementation may be beneficial when depletion is

severe or when the intestinal mucosa is damaged by chemo- and/or radiation therapy.95 Similarly,

arginine supplementation may be associated with a lower infectious risk and shorter hospital length of

stay, however, no currently available evidence support its use during critical illness.96

The n-3 fatty acids (present in fish oil preparations) have been shown to have anti-inflammatory

effects, while n-9 fatty acids (present in olive oil) have a neutral effect on inflammation, and n-6 fatty

acids (in soybean oil) appear to be proinflammatory.97 On the basis of low levels of n-3 fatty acids in

acute lung injury patients and the proinflammatory properties of n-6 fatty acids, the lipid profile of such

patients was hypothesized to contribute to worsening acute lung injury, and some initial studies

suggested that administration of high n-3 to n-6 fatty acid ratio formulas may benefit critically ill

patients.98,99 However, more recent, higher-quality studies have failed to show a beneficial effect of rich

in n-3 fatty acid preparations in either enteral or parenteral nutrition formulations.100,101 Currently, the

lack of high-quality evidence precludes any recommendation on the use of specific lipids in critically ill

patients.

13 Micronutrients, as electrolytes, vitamins and trace elements are generally termed, are

administered in critical illness to prevent deficiencies and associated complications. With repletion of

micronutrient stores after starvation, refeeding syndrome can occur, which typically unmasks severe

deficiencies in potassium, phosphate, and thiamine. This can be life-threatening and present with lactic

acidosis, cardiac arrhythmias, worsening respiratory failure, and even heart failure. Therefore, routine

administration of micronutrients during critical illness is commonly warranted. Provision of therapeutic

doses of trace elements (selenium, copper, zinc, and iron) and vitamins (E, C, and beta-carotene) with

antioxidant activity has also been proposed,102 however, recent randomized controlled data failed to

demonstrate a benefit.93 Selenium supplementation may also be beneficial in subjects with selenium

deficiency, and the potential benefit is supported by a recent meta-analysis.103

Current recommendations for nutritional support during critical illness are summarized on Table 3-12.

Access Routes

TPN solutions are administered through a central venous catheter, generally inserted in the subclavian

or internal jugular vein, or through peripherally inserted central catheters (PICCs) that are typically

inserted in veins of the antecubital fossa and have their ends reach the atriocaval junction.

Administration of TPN through femoral venous catheters is avoided as possible, due to the greater

incidence of infectious complications this access site entails. Central lines are preferred when short-term

central venous access is indicated, and are commonly inserted by surgeons, intensivists, or

interventional radiologists. In contrast, PICC lines are placed by specially trained nursing staff or

interventional radiologists, and the logistics of insertion (scheduling, availability, and workload of the

practitioners placing them) must be considered. The major benefit of PICCs is that patients can be

discharged from the hospital with them, if prolonged access is required, and their safer insertion profile,

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while the major advantage of traditional central venous catheters is that they allow infusion of

vasoactive medications, and can be used for resuscitative purposes (administration of large volume of

crystalloids rapidly) and advanced hemodynamic monitoring (measurement of central venous pressure).

Both carry multiple ports, and it is a common practice to save one of these for nutrition access alone, as

the high-carbohydrate concentration of nutrition solutions can act as a nidus for infection, if the same

port is used both for TPN administration and is frequently accessed for blood draws. Both devices can

also be used for administration of medications toxic to the peripheral venous system (e.g., hypertonic

saline, vancomycin, and other hyperosmolar solutions), and allow an easy access route for repeat

venous sampling, which can be convenient in patients requiring frequent laboratory draws. Routine

exchange of uncomplicated central or PICC lines is not advocated, and both types of catheters should be

removed when the indication for their placement ceases to exist, to minimize infectious and thrombotic

complications.

Table 3-12 Recommendations for Clinical Nutritional Practice in the ICU

Peripheral parenteral nutrition (PPN) can be infused through peripheral venous cannulas. Peripheral

intravenous feedings may be used for infusion of protein, lipid, and lower concentration dextrose

solutions. PPN is limited in caloric delivery, due to the large volumes it would require to meet daily

demands, but it avoids central venous cannulation, which has considerable complications. It can be

considered for short-term parenteral nutrition, for example, in the case of postoperative patients with

ileus expected to resolve in a few days.

Enteral feedings are typically administered through oro/naso-, -gastric or -enteric feeding tubes in the

acute phase of disease. The stomach is easily accessed with a soft flexible feeding tube. Intragastric

feedings provide several advantages compared to more distal gastrointestinal tract feedings, as the

stomach has the capacity and reservoir for bolus feedings. Feeding into the stomach stimulates the

biliary and pancreatic axis, with trophic benefits for the entire small bowel. Finally, gastric secretions

exert a dilutional effect on tube feeding osmolarity, reducing the risk of diarrhea. An important risk of

intragastric feedings is regurgitation of gastric contents with possible aspiration into the

tracheobronchial tree. This risk is highest in patients with altered mental status or who are paralyzed.

Placement of the feeding tube through the pylorus further down into the small bowel reduces the risk of

regurgitation. Nasoduodenal/nasojejunal tubes are smaller in caliber and therefore more comfortable

for patients, however, they are more prone to clogging. Patients who repeatedly remove their catheters

may be candidates for feeding tube bridles. Placement of nasogastric or nasoduodenal tubes should

always be confirmed radiographically prior to initiation of feedings.

Patients with chronically impaired mental status (such as those with severe traumatic brain injury),

an inadequate swallowing mechanism or dysphagia, and those with oropharyngeal or proximal

gastrointestinal tract pathology or recent/anticipated surgical procedure may be candidates for longer

term transabdominal gastrointestinal access. This access is typically provided through temporary Stamm

gastrostomies, in which a small laparotomy incision is made, and the gastric lumen in the midportion of

the gastric body is accessed, while a transabdominal large-bore feeding tube is secured in place with

concentric purse string sutures. Percutaneous endoscopic gastrostomy (PEG) tubes can be inserted and

provide access for gastric feedings, without the need for laparotomy, general anesthesia, and even a trip

to the operating room, as they can be performed at the bedside under endoscopic guidance. Using

monitored anesthesia care, a gastroscope is advanced transorally into the stomach and helps

transilluminate the anterior gastric wall through the abdominal wall. A small abdominal incision is

made over the area of maximal transillumination, ideally over the midportion of the gastric body, and

through an angiocath, a wire is advanced into the gastric lumen, which is snared and pulled back out of

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