In addition, the slower infusion rate associated with continuous infusion

may be better tolerated as judged by stool frequency and time to attain full nutrition

support, especially in the elderly and in metabolically unstable patients.

33–35

However, data were insufficient to include a recommendation for continuous infusion

versus other administration methods for critically ill patients in the CCP

guidelines.

18–20 Feeding into the duodenum or jejunum is best initiated with

continuous infusion because rapid infusion of large formula volumes into the small

bowel can result in symptoms of dumping syndrome, including sweating,

lightheadedness, abdominal distension, cramping, hyperperistalsis, and watery

diarrhea. With time, the jejunum may adapt to larger volumes over a shorter time

allowing cyclic or longer intermittent infusions.

Cyclic Feeding

Cyclic feeding provides formula at a continuous rate for less than 24 hours daily.

This method is most commonly used for patients who need supplemental nutrition

because of an inability to consume adequate oral nutrients, during transition to an oral

diet, and for long-term home EN patients. Infusions are typically given at night for 8

to 12 hours to minimize interference with oral intake and normal activities during the

day, although cycles can be as long as 20 hours. Most patients do not start on a cyclic

regimen; rather, they transition from continuous feeding. Formula volume and

osmolality can limit tolerance to cyclic feedings, especially jejunal feedings, and

transition from continuous to cyclic infusion may require several days to weeks

depending on patient tolerance. For gastric feeding, the transition usually takes only a

few days.

Intermittent and Bolus Feedings

Formula is provided in three to eight gastric feedings daily for intermittent and bolus

administration. Intermittent infusion occurs for 30 to 60 minutes using a feeding

container or bag, with or without an enteral pump, and bolus feedings are for about

15 minutes using gravity administration via a syringe.

34–37 The stomach’s reservoir

capacity allows administration of relatively large volumes on an intermittent or bolus

schedule. This is more physiologic than continuous feeding and more convenient for

patients in nursing facilities and ambulatory patients at home on EN.

INITIATION OF FEEDINGS

The regimen for initiating EN primarily depends on the site of feeding and condition

of the patient’s GI tract. Use of full-strength (i.e., undiluted) formula is recommended

for initiation of feedings.

34–37 Dilution delays delivery of adequate nutrients without

significantly affecting the incidence of GI intolerance. Hypertonic formulas are

diluted rapidly in the GI tract, reaching isotonicity before or shortly beyond the

ligament of Treitz (distal end of duodenum). Continuous feedings are commonly

initiated at a rate of 10 to 50 mL/hour with advancement by 10 to 25 mL/hour every 4

to 24 hours as tolerated, although stable patients may tolerate initiation of EN at goal

rate.

3,34,35 For critically ill patients, those with abnormal GI function, patients without

use of the GI tract for a prolonged time, those at risk of refeeding syndrome, and

when calorically dense or high-osmolality formulas are used, starting at the lower

rate and advancing slowly (i.e., start at 10–20 mL/hour and advance by 10–15

mL/hour every 12 or 24 hours) may be preferable, although this is based on

consensus rather than evidence from well-designed studies.

25,33–36

Patients are typically started on continuous infusion feedings, then transition to

intermittent infusions, and eventually to bolus feedings, if desired. Bolus feedings are

administered for about 15 minutes to avoid bloating, cramping, nausea, and diarrhea.

A rate of less than 60 mL/minute is suggested to minimize GI intolerance with bolus

feedings.

36,37 For intermittent feeding, rates of 200 to 300 mL every 4 to 6 hours are

generally tolerated; volumes up to 750 mL may be tolerated.

33,36,37

Initiation of

feedings at goal rate may be tolerated by some patients, although starting slower is

appropriate for most patients.

D.S. receives gastric feeds; therefore, continuous infusion, intermittent infusion, or

bolus feedings could all be used. Continuous infusion most commonly is used for

hospitalized patients despite no clearly established difference in tolerance compared

with intermittent infusion. Full-strength formula should be used to initiate feedings.

The goal volume of enteral nutrition for D.S. is 1,440 mL/day of a standard caloric

density formula (1.06 kcal/mL,

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0.44 g protein/mL, 83.5% free water), or 60 mL/hour continuous infusion. The

infusion could be started at 30 mL/hour (half goal rate); however, given D.S.’s risk

for refeeding syndrome, it is preferable to start slower. Starting at 15 mL/hour for 12

hours, then increasing by 15 mL/hour every 12 hours would achieve the goal rate of

60 mL/hour within 48 hours. If D.S. experiences diarrhea or abdominal distension,

the feeding may be held at 15 mL/hour for 24 hours, then increased by only 10

mL/hour every 12 to 24 hour as tolerated. Extra care is required to ensure he

receives an adequate fluid intake until the formula is at goal rate.

Continuous infusion enteral feeding can be administered by gravity drip or by

enteral pump. With gravity drip, the infusion rate must be adjusted frequently to

maintain a consistent flow rate, and formula flow must be checked regularly to ensure

that the flow has not stopped. Gravity infusion has no alarms to alert nurses to kinked

tubing or empty delivery containers. Enteral pumps provide a consistent flow rate

and alarms for problems with the infusion, but they are more expensive than gravity

drips. Pumps often are used for hospitalized patients to help maintain delivery of the

prescribed volume of enteral formula. Either gravity drip or an enteral pump could

be used for D.S., depending on the hospital’s protocol for enteral feeding.

To prevent potentially fatal inadvertent IV infusion of non-IV products, new non-

Luer compatible global design standards for small-bore liquid and gas medical

device tubing connectors, including enteral feeding connectors, are being introduced

under the “Stay Connected” initiative.

38 The connection between the enteral formula

bag and the tubing going into the bag changed in 2012. Transition to the new ENFit

connector between the administration tubing and feeding tube itself is expected to be

completed by 2016. Oral syringes will not fit the new ENFit connectors; therefore,

ENFit compatible syringes are required for medication administration, tube flushes,

and bolus feeding via syringe.

TRANSITION FROM CONTINUOUS TO

INTERMITTENT/BOLUS FEEDING

CASE 37-2, QUESTION 7: D.S. has received EN for 10 days. He has tolerated his continuous tube feeding

without problems and has not required electrolyte replacements for the past 4 days. The plan is to transfer D.S.

to a skilled nursing facility (SNF) in the next few days. The SNF requests D.S. be on an intermittent/bolus

feeding regimen before transfer to the SNF. How should D.S. be changed from continuous infusion to

intermittent or bolus feeding?

Many nursing facilities do not routinely use enteral pumps because of increased

cost. Without a pump, delivery of the prescribed volume of formula at a consistent

rate may not be reliable and increased nursing time may be required to prevent tube

occlusion and ensure adequate volume of formula is delivered. D.S. is currently

receiving continuous infusion feedings. The transition to intermittent delivery of

formula can be accomplished by various methods. An overlapping regimen of

gradually decreasing the continuous infusion rate and increasing the intermittent

volume appears to be an economical and efficient method of changing the feeding

regimen.

33 For D.S., decrease the continuous rate from 60 mL/hour down to 40

mL/hour and add four intermittent feedings of 120 mL over 60 minutes every 6 hours

initially. If tolerated, decrease continuous infusion to 20 mL/hour and increase

intermittent feeding to 240 mL. Finally, stop the continuous feeding and increase

intermittent feedings to 360 mL, or add a fifth feeding to keep the intermittent volume

at 285 to 300 mL. To keep the feeding volume in a more convenient increment of 120

mL (half of an 8-ounce can), D.S. could receive two feedings of 360 mL and three

feedings of 240 mL if five daily feedings are needed.

Another transition method is to stop continuous feedings and restart feedings with a

regimen for initiating intermittent feedings. Starting volume is typically 60 to 120 mL

for the first two or three feedings, and feeding intervals are often every 4 hours.

Volume is increased by 60 to 120 mL every 8 to 12 hours, as tolerated, until goal is

reached.

35 Feeding intervals can be increased once goal volume is reached. D.S.

could start with 120 mL over 60 minutes every 4 hours for two feedings, then

advance to 240 mLper feeding. If tolerated, the volume per feeding could increase to

360 mL to allow feedings every 6 hours. Once at the desired number of feedings per

day, the infusion time could be decreased based on tolerance. If feeding for 30

minutes is well tolerated, D.S. could be changed to bolus administration for 15 to 20

minutes.

The discharge EN prescription should state clearly the desired caloric density,

protein content, fiber content per 1,000 kcal, and formula volume, or the daily

calories, protein, fiber, and fluid goals. The brand name may be included, but the

SNF may not carry the same brand of formula. Any special considerations for the

feeding schedule also should be communicated (e.g., D.S. does not tolerate feeding

after 9 PM; raise the head of the bed to 45 degrees for 3 hours after the last daily

feeding to avoid regurgitation).

FLUID PROVISION

CASE 37-2, QUESTION 8: How much additional fluid must be included in the feeding regimen to meet

D.S.’s estimated daily fluid requirements?

The free-water content of EN must be calculated to determine the volume of

additional fluid that must be provided. As noted previously, standard caloric density

formulas generally contain 80% to 85% free water. The formula selected for D.S.

contains 83.5% free water; therefore, at his goal volume of 1,440 mL/day (six cans),

the formula provides approximately 1,200 mL of free water daily. Using 1,860 mL

daily (30 mL/kg/day × 62 kg) as D.S.’s fluid requirement (see Case 37-2, Question

5), he will need 660 mL/day in addition to the enteral formula. If D.S. had additional

losses from vomiting, diarrhea, or other sources, this volume would be added to the

660 mL to determine total volume in addition to enteral formula. The additional fluid

is typically provided with medications and tube irrigation (flushes). Feeding tubes

should be irrigated with 30 mL of fluid every 4 hours during continuous feeding, or

before and after each intermittent or bolus feeding.

34,35 The tube should be flushed

with a minimum of 15 mL of water before and after medication administration

through the tube, as well as with 15 mL between each medication.

34–37 Fluid also is

required for diluting medications before administration through the tube. The flush

volume and/or number of flushes will need to be increased to provide D.S. with

adequate fluid because 30 mL every 4 hours plus fluid for medication administration

will not provide the 660 mL of fluid needed in addition to his EN. Because D.S. is

receiving gastric feedings, hypotonic fluid is of less concern than in the jejunum.

39

Increasing flush volumes to between 100 and 150 mL should meet D.S.’s daily fluid

requirement, depending on the amount needed for medication administration. Diluting

the formula itself to increase fluid provision is not recommended because this

increases the risk of error and contamination.

NUTRITION IN CRITICAL ILLNESS

Nutrition support is an important component of care in critical illness where patients

are typically in a catabolic stress state and

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metabolism may be altered. Multiorgan dysfunction, as well as fluid and electrolyte

imbalances, adds to the complexity of this population and confounds attempts to

provide proper nutrition. The preferred route for nutrition support is generally EN,

although the ideal formula composition remains unresolved. Guidelines are

periodically updated. The most recently published guidelines should be consulted to

determine current recommendations, especially regarding specialized components

discussed in this section.

CASE 37-3

QUESTION 1: J.B., a 68-year-old man with a past medical history of hypertension, presents to the ED with

complaints of shortness of breath, productive cough, wheezing, and fever. J.B. subsequently requires intubation

and is transferred to the ICU with a diagnosis of pneumonia. During the next 24 hours, his respiratory status

further declines, and he is diagnosed with acute respiratory distress syndrome (ARDS). In anticipation of a

prolonged course of mechanical ventilation, a feeding tube is placed into the small bowel. The chart indicates a

height of 70 inches and an admission weight of 75 kg.

Laboratory evaluation today includes the following:

Sodium, 140 mEq/L

Potassium, 3.9 mEq/L

Chloride, 109 mEq/L

Carbon dioxide content, 22 mM

BUN, 18 mg/dL

SCr, 0.8 mg/dL

Glucose, 118 mg/dL

Albumin, 3.6 g/dL

Aspartate aminotransferase, 32 international units/L

Alanine aminotransferase, 37 international units/L

Alkaline phosphatase, 64 international units/L

Total bilirubin, 0.7 mg/dL

WBC, 15.3 × 10

3

/μL

Hgb, 13.4 g/dL

Hct, 39.9%

Should a specialized critical care formula be used for initiation of EN in J.B.?

J.B. is critically ill and several types of EN formulas have been developed for

critically ill patients. However, the role of specialized EN formulas, and certain

components in particular, remains controversial in critical illness. Table 37-4 shows

a few formulas marketed for critical illness and lists the components which are

altered compared to standard polymeric formulas. Due to the catabolic nature of

critical illness, formulas are generally high protein, many with an NPC:N ratio less

than 100:1 (i.e., high or very high protein content). Other formulas containing slightly

lower-protein content (i.e., NPC:N ratio between 100:1 and 125:1) target the

inflammatory element of critical illness with addition of components designed to

mitigate the inflammatory response. Formulas designed for critical illness are

typically fiber-free, although a few formulas include small amounts of soluble fiber.

Supplementation of specific amino acids, including branched-chain amino acids

(BCAAs), glutamine, and arginine, in EN for critical illness remains an unsettled

issue.

Enhanced Branched-Chain Amino Acid Content

Standard EN formulas contain 15% to 20% of protein as BCAAs; enhanced BCAA

formulas for critical care contain over 35%, and hepatic failure formulas contain

45% to 50%. High-BCAA stress/critical care formulas are not therapeutically

interchangeable with hepatic formulas due to the lower-than-normal concentrations of

aromatic amino acids (AAAs), especially phenylalanine, in hepatic formulas.

Guidelines from SCCM–ASPEN recommend a standard enteral formula for

patients with acute or chronic liver disease in the ICU.

4 High–very high protein is

currently emphasized over BCAA content for critically ill patients.

Glutamine

The proposed role of glutamine in critical illness is enhanced neutrophil function and

maintenance of intestinal barrier function, thereby preventing translocation of

bacteria and endotoxins from the GI tract into systemic circulation and reducing

bacteremia.

40 Glutamine is considered a nonessential amino acid, as it is synthesized

in sufficient quantities for its roles in transamination, as an intermediate in numerous

metabolic pathways, such as gluconeogenesis and renal ammoniagenesis, as a fuel

source for rapidly dividing lymphocytes and enterocytes, and in the synthesis of

glutathione. However, during periods of metabolic stress, endogenous synthesis may

become inadequate.

Study results are conflicting regarding effects of glutamine supplementation in the

critically ill population. Past studies have indicated numerous clinical benefits from

glutamine supplementation; however, two recent studies (REDOXs, METAPLEX)

suggest increased mortality in critically ill patients receiving parenteral and/or

enteral glutamine.

41–44 The CCP guidelines now recommend against the use of enteral

glutamine in critically ill patients.

19 Glutamine supplementation should also be

avoided in patients with total bilirubin greater than 10 mg/dL or creatinine clearance

less than 30 mL/minute because ammonia excretion could be impared.

45 Monitoring

for potential complications is essential when glutamine supplementation is used.

Protein-bound glutamine is present in all enteral formulas. Free glutamine is

unstable in ready-to-use formulas and, due to poor stability, is not commercially

available in an intravenous form. However, glutamine is available as a modular

supplement, which can be administered separately from the EN formula. Glutamate is

stable in water and functions in many roles attributed to glutamine. Additional

research is needed to determine whether physiologic effects are equivalent for

glutamate, protein-bound glutamine, and free glutamine.

Arginine

Arginine is a nonessential amino acid synthesized by the urea cycle during

detoxification of ammonia and is normally available in sufficient quantities for

growth and tissue repair. In times of metabolic stress, however, endogenous synthesis

may become inadequate, making arginine conditionally essential. The postulated

benefit of arginine in critical illness is related to enhanced protein synthesis, cellular

growth, and immune system support. In contrast, several mechanisms have been

proposed that suggest potential adverse effects with arginine supplementation,

including one in which arginine is used as a substrate in the synthesis of nitric oxide

(NO), a potent vasodilating agent, which may also have implications in mitochondria

damage, organ dysfunction, and increased gut barrier permeability.

46 Although

synthesis of NO increases during sepsis (thereby creating a negative arginine

balance), the exact role of this effector molecule remains controversial. Many

believe that excess NO is part of an adaptive response directed toward limiting

infection, ischemia, coagulation, inflammation, and tissue injury.

Conflicting study results leave considerable uncertainty regarding use of arginine

supplemented EN in critically ill patients.

4,18–20

,

47 Guidelines, consensus statements,

and recommendations have been developed to help the clinician provide evidencebased nutrition therapy; however, many barriers to implementation exist.

4,18–20

,

48,49

Use of arginine-containing, immune-enhancing diets is not recommended for

critically ill patients in the CCP guidelines because higher-quality studies indicated

no effect on mortality with these formulas and increased mortality was reported for

septic patients in some studies.

18–20

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Table 37-4

Selected High-Protein Enteral Formulas with Altered Protein or Fat Sources

Free Protein

Fat

g/L

Formula

a

,

b

,

c

kcal/mL

(mOsm/kg)

Water

(%)

g/L (%

kcal) NPC:N

Protein

Source

ARG

g/L

d

GLN

g/L

d

(%

kcal) Fat Sources

Crucial

c 1.5 (490) 77 94 (25) 67:1 Hydrolyzed

casein; Larginine

15 – 67.6

(39)

MCT oil; fish

oil (<2%);

soybean oil;

lecithin

50

f.a.a

c 1.0 (850) 85 50 (20) 100:1 Crystalline

amino acids

– – 11.2

(10)

Soybean oil;

MCT

25

Impact with

Fiber

c

1.0 (375) 87 56 (22) 71:1 Sodium and

calcium

caseinates;

L-arginine

12.5 – 28

(25)

Palm kernel

oil; menhaden

oil

–

Impact 1.5

c 1.5 (550) 78 84 (22) 71:1 Sodium and

calcium

caseinates;

L-arginine

18.7 – 69

(40)

MCT; palm

kernel oil;

menhaden oil

33

Impact

Glutamine

c

1.3 (630) 81 78 (24) 62:1 Whey

protein

hydrolysate;

free amino

acids;

sodium

caseinates;

L-arginine

16.3 15 43

(30)

Palm kernel

oil; menhaden

oil

–

Optimental

b 1.0 (540) 83.2 51

(20.5)

97:1 Soy protein

hydrolysate;

partially

hydrolyzed

sodium

caseinate;

L-arginine

5.5 – 28.4

(25)

Structured

lipid

(interesterified

sardine oil

[EPA, DHA]

and MCT);

canola oil; soy

oil

NA

Osmolite 1.2

Cal

b

1.2 (360) 82 55.5

(18.5)

110:1 Sodium and

calcium

caseinate

– – 39

(29)

High-oleic

safflower oil;

canola oil;

MCT oil;

lecithin

20

Oxepa

b 1.5 (535) 78.5 62.5

(16.7)

125:1 Sodium and

calcium

caseinates

– – 93.8

(55)

Canola oil;

MCT oil;

sardine oil;

borage oil

25

Peptamen

AF

c

1.2 (390) 81 75.6

(21)

76:1 Hydrolyzed

whey

protein

– – 54.8

(39)

MCT oil;

soybean oil

(<2%); fish oil

(<2%);

lecithin

50

Pivot 1.5

Cal

b

1.5 (595) 75.9 93.8

(25)

75:1 Partially

hydrolyzed

sodium

caseinate;

whey

protein

13 6.5 50.8

(30)

Structured

lipid

(interesterified

sardine oil

[EPA, DHA]

and MCT);

20

hydrolysate soy oil; canola

oil

aChanges periodically occur in nutrient sources and content; use this table as a general reference only and not for

specific patient care issues.

bAbbott (Ross) product.

cNestle product.

dNone or unknown indicated by “–.”

AF, advanced formula; ARG, arginine; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FOS,

fructooligosaccharides; GLN, glutamine; MCT, medium-chain triglycerides; NPC:N, nonprotein calorie to nitrogen;

ω-3FA, ω-3 fatty acids; ω-6FA, ω-6 fatty acids.

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IMMUNE-MODULATING FORMULAS

Formulas included in Table 37-4 have an NPC:N ratio less than or equal to 125:1

and also contain supplemental arginine, glutamine, or nucleic acids, or a modified fat

component. Such formulas are often referred to as “immune-modulating” formulas

based on their proposed beneficial modulation of biologic responses to stress. Study

formulas frequently contain varying portions of two or more potentially immunemodifying components, making it difficult to determine the effect of any given

component. The subset of immune-modulating formulas intended for patients with

acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is distinct

from other formulas and is discussed in more detail under pulmonary disease.

The results of clinical trials examining the effects of immune-modulating enteral

formulations on mortality, hospital length of stay (LOS), ICU days, incidence of

nosocomial infection, duration of mechanical ventilation, and GI complications are

conflicting.

4,18–20