Artigo Parenteral Usos

Journal of Parenteral and
Enteral Nutrition
Volume 33 Number 3
Guidelines for the Provision and

May/June 2009 277-316
© 2009 American Society for
Parenteral and Enteral Nutrition and
Assessment of Nutrition Support Therapy Society of Critical Care Medicine

10.1177/0148607109335234
in the Adult Critically Ill Patient:

http://jpen.sagepub.com
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http://online.sagepub.com
Society of Critical Care Medicine (SCCM) and American

Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)
Stephen A. McClave, MD; Robert G. Martindale, MD, PhD;
Vincent W. Vanek, MD; Mary McCarthy, RN, PhD; Pamela Roberts, MD;
Beth Taylor, RD; Juan B. Ochoa, MD; Lena Napolitano, MD; Gail Cresci, RD;
the A.S.P.E.N. Board of Directors; and the American College of Critical Care Medicine
Preliminary Remarks Periodic Guideline Review and Update

These guidelines may be subject to periodic review and
Guideline Limitation revision based on new peer-reviewed critical care nutri-
Practice guidelines are not intended as absolute require- tion literature and practice.
ments. The use of these practice guidelines does not in
any way project or guarantee any specific benefit in out- Target Patient Population for Guideline
come or survival.
The judgment of the healthcare professional based on These guidelines are intended for the adult medical and
individual circumstances of the patient must always take surgical critically ill patient populations expected to
precedence over the recommendations in these guidelines. require an ICU stay of > 2 or 3 days and are not intended
The guidelines offer basic recommendations that are for those patients in the ICU for temporary monitoring or
supported by review and analysis of the pertinent available those who have minimal metabolic or traumatic stress.
current literature, by other national and international These guidelines are based on populations, but like any
guidelines, and by the blend of expert opinion and clinical other therapeutic treatment in an ICU patient, nutrition
practicality. The “intensive care unit” (ICU) or “critically requirements and techniques of access should be tailored
ill” patient is not a homogeneous population. Many of the to the individual patient.
studies on which the guidelines are based are limited by
sample size, patient heterogeneity, variability in definition Target Audience
of disease state and severity of illness, lack of baseline
nutrition status, and lack of statistical power for analysis. The intended use of these guidelines is for all individuals
Whenever possible, these factors are taken into account involved in the nutrition therapy of the critically ill, pri-
and the grade of statement will reflect the power of the marily physicians, nurses, dietitians, pharmacists, and
data. One of the major methodological problems with any respiratory and physical therapists where indicated.
guideline is defining the exact population to be included.
Methodology
A list of guideline recommendations was compiled by the
Address correspondence to: Steven A. McClave, MD, Division experts on the Guidelines Committee for the 2 societies,
of Gastroenterology/Hepatology, University of Louisville, 550
South Jackson Street, Louisville, KY 40292; email: samcclave@ each of which represented clinically applicable definitive
louisville.edu. statements of care or specific action statements. Prospec
These guidelines are also being co-published by the Society of tive randomized controlled trials were used as the primary
Critical Care Medicine (SCCM) in Critical Care Medicine, source to support guideline statements, with each study
2009; volume 37, number 5. being evaluated and given a level of evidence. The overall
277
278 Journal of Parenteral and Enteral Nutrition / Vol. 33, No. 3, May/June 2009
Table 1. Grading System Used for These Guidelines

Grade of recommendation
A Supported by at least two level I investigations
B Supported by one level I investigation
C Supported by level II investigations only
D Supported by at least two level III investigations
E Supported by level IV or level V evidence
Level of evidence
I Large, randomized trials with clear-cut results; low risk of false-positive (alpha) error or false-negative (beta) error
II Small, randomized trials with uncertain results; moderate to high risk of false-positive (alpha)
and/or false-negative (beta) error
III Nonrandomized, contemporaneous controls
IV Nonrandomized, historical controls
V Case series, uncontrolled studies, and expert opinion
Note: Large studies warranting level I evidence were defined as those with ≥100 patients or those which fulfilled end point criteria
predetermined by power analysis. Meta-analyses were used to organize information and to draw conclusions about overall treatment
effect from multiple studies on a particular subject. The grade of recommendation, however, was based on the level of evidence of
the individual studies.
Reproduced from Dellinger RP, Carlet JM, Masur H. Introduction. Crit Care Med. 2004;32(11)(suppl):S446 with permission of the
publisher. Copyright 2004 Society of Critical Care Medicine.
grade for the recommendation was based on the number Introduction

and level of investigative studies referable to that guide-
line. Large studies warranting level I evidence were The significance of nutrition in the hospital setting can-
defined as those with ≥100 patients or those which ful- not be overstated. This significance is particularly noted
filled endpoint criteria predetermined by power analysis. in the ICU. Critical illness is typically associated with a
The level of evidence for uncontrolled studies was deter- catabolic stress state in which patients commonly demon-
mined by whether they included contemporaneous con- strate a systemic inflammatory response. This response is
trols (level III), historical controls (level IV), or no coupled with complications of increased infectious mor-
controls (level V, equal to expert opinion). See Table 1.1 bidity, multi-organ dysfunction, prolonged hospitaliza-
Review papers and consensus statements were considered tion, and disproportionate mortality. Over the past 3
expert opinion and were designated the appropriate level decades, the understanding of the molecular and biologi-
of evidence. Meta-analyses were used to organize the cal effects of nutrients in maintaining homeostasis in the
information and to draw conclusions about an overall critically ill population has made exponential advances.
treatment effect from multiple studies on a particular Traditionally, nutrition support in the critically ill popula-
subject. The grade of recommendation, however, was tion was regarded as adjunctive care designed to provide
based on the level of evidence of the individual studies. exogenous fuels to support the patient during the stress
An A or B grade recommendation required at least 1 or 2 response. This support had 3 main objectives: to preserve
large positive randomized trials supporting the claim, lean body mass, to maintain immune function, and to
while a C grade recommendation required only 1 small avert metabolic complications. Recently these goals have
supportive randomized investigation. The rationale for become more focused on nutrition therapy, specifically
each guideline statement was used to clarify certain attempting to attenuate the metabolic response to stress,
points from the studies, to identify controversies, and to to prevent oxidative cellular injury, and to favorably mod-
provide clarity in the derivation of the final recommenda- ulate the immune response. Nutritional modulation of
tion. Significant controversies in interpretation of the the stress response to critical illness includes early enteral
literature were resolved by consensus of opinion of the nutrition, appropriate macro- and micronutrient delivery,
committee members, which in some cases led to a down- and meticulous glycemic control. Delivering early
grade of the recommendation. Following an extensive nutrition support therapy, primarily using the enteral
review process by external reviewers, the final guideline route, is seen as a proactive therapeutic strategy that may
manuscript was reviewed and approved by A.S.P.E.N. reduce disease severity, diminish complications, decrease
Board of Directors and SCCM's Board of Regents and length of stay in the ICU, and favorably impact patient
Council. outcome.
Guidelines for Nutrition Support Therapy / McClave et al 279
A. Initiate Enteral Feeding therapy” refers to a patient’s own volitional intake without
provision of specialized nutrition support therapy. The
A1. Traditional nutrition assessment tools (albumin,
importance of promoting gut integrity with regard to patient
prealbumin, and anthropometry) are not validated in
outcome is being strengthened by clinical trials comparing
critical care. Before initiation of feedings, assessment
critically ill patients fed by EN to those receiving standard
should include evaluation of weight loss and previous
(STD) therapy. In a recent meta-analysis10 in elective gas-
nutrient intake prior to admission, level of disease
trointestinal surgery and surgical critical care, patients
severity, comorbid conditions, and function of the
undergoing a major operation who were given early postop-
gastrointestinal (GI) tract. (Grade: E)
erative EN experienced significant reductions in infection
(relative risk [RR] = 0.72; 95% confidence interval [CI]
Rationale. In the critical care setting, the traditional pro-
0.54-0.98; P = .03), hospital length of stay (mean 0.84 days;
tein markers (albumin, prealbumin, transferrin, retinol
range 0.36-1.33 days; P = .001), and a trend toward reduced
binding protein) are a reflection of the acute phase
anastomotic dehiscence (RR = 0.53; 95% CI 0.26-1.08; P =
response (increases in vascular permeability and repriori-
.08), when compared to similar patients receiving no nutri-
tization of hepatic protein synthesis) and do not accu-
tion support therapy.10-16 In a meta-analysis17 of patients
rately represent nutrition status in the ICU setting.
undergoing surgery for complications of severe acute pan-
Anthropometrics are not reliable in assessment of nutri-
creatitis, those placed on EN 1 day postop showed a trend
tion status or adequacy of nutrition therapy.2,3
toward reduced mortality compared to controls randomized
A2. Nutrition support therapy in the form of enteral to STD therapy (RR = 0.26; 95% CI 0.06-1.09; P = .06).17-19
nutrition (EN) should be initiated in the critically ill See Table 2.11-16,18,19
patient who is unable to maintain volitional intake.
(Grade: C) A3. EN is the preferred route of feeding over paren-
teral nutrition (PN) for the critically ill patient who
Rationale. EN supports the functional integrity of the gut by requires nutrition support therapy. (Grade: B)
maintaining tight junctions between the intraepithelial cells,
stimulating blood flow, and inducing the release of trophic Rationale. In the majority of critically ill patients, it is
endogenous agents (such as cholecystokinin, gastrin, bomb- practical and safe to utilize EN instead of PN. The ben-
esin, and bile salts). EN maintains structural integrity by eficial effects of EN when compared to PN are well
maintaining villous height and supporting the mass of documented in numerous prospective randomized con-
secretory IgA-producing immunocytes which comprise the trolled trials involving a variety of patient populations in
gut-associated lymphoid tissue (GALT) and in turn contri critical illness, including trauma, burns, head injury,
bute to mucosal-associated lymphoid tissue (MALT) at major surgery, and acute pancreatitis.8,20-22 While few
distant sites such as the lungs, liver, and kidneys.4-7 studies have shown a differential effect on mortality, the
Adverse change in gut permeability from loss of func- most consistent outcome effect from EN is a reduction
tional integrity is a dynamic phenomenon which is time- in infectious morbidity (generally pneumonia and central
dependent (channels opening within hours of the major line infections in most patient populations, and specifi-
insult or injury). The consequences of the permeability cally abdominal abscess in trauma patients).20 In many
changes include increased bacterial challenge (engage- studies, further benefits are seen from significant reduc-
ment of GALT with enteric organisms), risk for systemic tions in hospital length of stay,21 cost of nutrition
infection, and greater likelihood of multi-organ dysfunc- therapy,21 and even return of cognitive function (in head
tion syndrome (MODS).4,5 As disease severity worsens, injury patients).23 All 6 meta-analyses that compared
increases in gut permeability are amplified and the enteral EN to PN showed significant reductions in infectious
route of feeding is more likely to favorably impact out- morbidity with use of EN.21,24-28 Noninfective complica-
come parameters of infection, organ failure, and hospital tions (risk difference = 4.9; 95% CI 0.3-9.5; P =.04) and
length of stay (compared to the parenteral route).8 reduced hospital length of stay (weighted mean differ-
The specific reasons for providing early EN are to ence [WMD] = 1.20 days; 95% CI 0.38-2.03; P = .004)
maintain gut integrity, modulate stress and the systemic were seen with use of EN compared to PN in 1 meta-
immune response, and attenuate disease severity.6,8,9 analysis by Peter et al.28 Five of the meta-analyses showed
Additional endpoints of EN therapy include use of the gut no difference in mortality between the 2 routes of nutri-
as a conduit for the delivery of immune-modulating tion support therapy.21,24,26-28 One meta-analysis by
agents and use of enteral formulations as an effective Simpson and Doig25 showed a significantly lower mortality
means for stress ulcer prophylaxis. (RR = 0.51; 95% CI 0.27-0.97; P =.04) despite a signifi-
Nutrition support therapy (also called “specialized” or cantly higher incidence of infectious complications
“artificial” nutrition therapy) refers to the provision of (RR = 1.66; 95% CI 1.09-2.51; P =.02) with use of PN
enteral tube feeding or parenteral nutrition. “Standard compared to EN.25 See Table 3.8,20,22,29-61
Table 2. Randomized Studies Evaluating Enteral Nutrition (EN) vs No Nutrition Support Therapy (Standard [STD]
Therapy) in Elective Surgery, Surgery Critical Care, and Acute Pancreatitis Patients
Hospital LOS
Study Days, Mean ± SD Hospital
Study Population Groups Infectiona (or Range) Mortality Other Outcomes
Sagar et al, 197912 GI surgery EN 3/15 (20%) 14 (10-26) 0/15 (0%)
Level II (n = 30) STD 5/15 (33%) 19 (10-46) 0/15 (0%)
Schroeder et al, 199111 GI surgery Anastomotic dehiscence
Level II (n = 32) EN 1/16 (6%) 0±4 0/16 (0%) 0/16 (0%)
STD 0/16 (0%) 15 ± 10 0/16 (0%) 0/16 (0%)
Carr et al, 199613 GI surgery Lactulose:mannitol ratio
Level II (n = 28) EN 0/14 (0%) 9.8 ± 6.6 0/14 (0%) 0.1 ± 0.03b
STD 3/14 (21%) 9.3 ± 2.8 1/14 (7%) 0.5 ± 0.26
Beier-Holgersen et al, GI surgery Anastomotic leak
199614 (n = 60) EN 2/30b (7%) 8.0c 2/30 (7%) 2/30 (7%)
Level II STD 14/30 (47%) 11.5 4/30 (13%) 4/30 (13%)
Heslin et al, 199715 GI surgery Major complication
Level I (n = 195) EN 20/97 (21%) 11 (4-41) 2/97 (2%) 27/97 (28%)
STD 23/98 (23%) 10 (6-75) 3/98 (3%) 25/98 (26%)
Watters et al, 199716 GI surgery Anastomotic leak
Level II (n = 28) EN NR 17 ± 9 0 (0%) 1/13 (8%)
STD 16 ± 7 0 (0%) 3/15 (20%)
Pupelis et al, 200018 Acute EN 3/11 (27%) 45 ± 96 1/11 (9%)
Level II pancreatitis STD 1/18 (6%) 29 ± 103 5/18 (28%)
(n = 29)
Pupelis et al, 200119 Acute MOF
Level II pancreatitis, EN 10/30 (33%)d 35.3 ± 22.9 1/30 (3%) 18/30 (60%)
peritonitis STD 8/30 (27%) 35.8 ± 32.5 7/30 (23%) 20/30 (67%)
(n = 60)
SD, standard deviation; NR, not reported; LOS, length of stay; GI, gastrointestinal; MOF, multiple organ failure.
a
All infections represent number of patients per group with infection unless otherwise stated.
b
P ≤ .05.
c
P = .08.
d
Wound sepsis.
A4. Enteral feeding should be started early within the reductions in infectious morbidity (RR = 0.45; 95% CI
first 24-48 hours following admission. (Grade: C) The 0.30-0.66; P = .00006) and hospital length of stay (mean
feedings should be advanced toward goal over the next 2.2 days, 95% CI 0.81-3.63 days; P = .001) with early EN
48-72 hours. (Grade: E) compared to delayed feedings.62 See Table 4.63-72
Rationale. Attaining access and initiating EN should be A5. In the setting of hemodynamic compromise
considered as soon as fluid resuscitation is completed and (patients requiring significant hemodynamic support
the patient is hemodynamically stable. A “window of including high dose catecholamine agents, alone or in
opportunity” exists in the first 24-72 hours following combination with large volume fluid or blood product
admission or the onset of a hypermetabolic insult. resuscitation to maintain cellular perfusion), EN
Feedings started within this time frame (compared to should be withheld until the patient is fully resusci-
feedings started after 72 hours) are associated with less tated and/or stable. (Grade: E)
gut permeability, diminished activation, and release of
inflammatory cytokines (ie, tumor necrosis factor [TNF] Rationale. At the height of critical illness, EN is being
and reduced systemic endotoxemia).21 One meta-analysis provided to patients who are prone to GI dysmotility,
by Heyland et al showed a trend toward reduced infec- sepsis, and hypotension and thus are at increased risk
tious morbidity (RR = 0.66; 95% CI 0.36-1.22; P =.08) for subclinical ischemia/reperfusion injury involving the
and mortality (RR = 0.52; 95% CI 0.25-1.08; P = .08),21 intestinal microcirculation. Ischemic bowel is a rare com-
while a second by Marik and Zaloga showed significant plication of EN, occurring in <1% of cases.73,74 EN-related
Table 3. Randomized Studies Evaluating Enteral Nutrition (EN) vs Parenteral Nutrition (PN)
in Surgery, Trauma, Pancreatitis, and Critically Ill Patients
LOS Days, Mean ± Other Clinical
Study Population Study Groups ICU Mortality Infectionsa SD (or Range) Outcomes Cost
Rapp et al, 198329 ICU head injury Duration MV NR
Level II (n = 38) EN 9/18 (50%)b NR 49.4 Hosp 10.3 d
PN 3/20 (15%) 52.6 Hosp 10.4 d
Adams et al, 198630 Trauma Duration MV
Level II (n = 46) EN 1/23 (4%) 15/23 (65%) 30 ± 21 Hosp 12 ± 11 d $1346/db
PN 3/23 (13%) 17/23 (74%) 31 ± 29 Hosp 10 ± 10 d $3729/d
EN 13 ± 11 ICU
PN 10 ± 10 ICU
Bower et al, 198631 GI surgery Complications
Level II (n = 20) EN 0/10 (0%) 0/10 (0%) 0/10 (0%)
PN 0/10 (0%) 0/10 (0%) 0/10 (0%)
Szeluga et al, 198732 Bone marrow No difference at 100 Complications
Level II transplant EN days and long-term 5/30 (17%) 33 ± 15 Hosp 11/30 (37%) $1139/patient
(n = 61) PN 8/31 (26%) 36 ± 18 Hosp 14/31 (45%) $2575/patient
Young et al, 198733 ICU head injury EN 10/28 (36%) 5/28 (18%) NR NR NR
Level II (n = 58) PN 10/23 (43%) 4/23 (17%)
Peterson et al, 198834 Trauma EN NR 2/21 (10%) 13. 2 ± 1.6 Hosp NR NR
Level II (n = 59) PN 8/25 (32%) 14.6 ± 1.9 Hosp
EN 3.7 ± 0.8 ICU
PN 4.6 ± 1.0 ICU
Cerra et al, 198835 ICU Complications
Level II (n = 70) EN 7/33 (21%) 0/33 (0%) NR 7/33 (21%) $228 ± 59/db
PN 8/37 (22%) 0/37 (0%) 7/37 (19%) $330 ± 61/d
Greenburg et al, 198836 Inflammatory Complications
Level II bowel (n = 51) EN 0/19 (0%) 0/19 (0%) 0/19 (0%)
PN 0/32 (0%) 0/32 (0%) 0/32 (0%)
Moore et al, 198937 Trauma (n = 75) EN 0/29 (0%) 5/29 (17%) NR NR
Level II PN 0/30 (0%) 11/30 (37%)
Hamaoui et al, 199038 GI surgery EN 1/11 (9%) 1/11 (9%) 0/11 (0%) $44.36/db
Level II (n = 19) PN 0/8 (0%) 0/8 (0%) 0/8 (0%) $102.10/d
Kudsk et al, 199220 Trauma (n = 98) Duration MV NR
Level II EN 1/51 (2%) 9/51 (18%)b 20.5 ± 19.9 Hosp 2.8 ± 4.9 d
PN 1/45 (2%) 18/45 (40%) 19.6 ± 18.8 Hosp 3.2 ± 6.7 d
González-Huix et al, Inflammatory Complications
199339 bowel (n = 44) EN 0/23 (0%) 1/23 (4%) 11/23 (48%)
Level II PN 0/21 (0%) 8/21 (38%) 11/21 (52%)
(continued)
281
Table 3. (continued)
282
LOS Days, Mean ± Other Clinical
Study Population Study Groups ICU Mortality Infectionsa SD (or Range) Outcomes Cost
Iovinelli et al, 199340 Head–neck Complications
Level II cancer EN 0/24 (0%) 5/24 (21%) 26 ± 11b Hosp 1/24 (4%)
(n = 48) PN 0/24 (0%) 4/24 (17%) 34 ± 11 Hosp 2/24 (8%)
Kudsk et al, 199441 Trauma (n = 68) Complications
Level II EN 1/34 (3%) 5/34 (15%) 0/34 (0%)
PN 0/34 (0%) 14/34 (41%) 0/34 (0%)
Dunham et al, 199442 Trauma (n = 37) NR Complications NR
Level II EN 1/12 (8%) 0/12 (0%) 0/12 (0%)
PN 1/15 (7%) 0/15 (0%) 0/15 (0%)
Borzotta et al, 199443 Neurotrauma EN 5/28 (18%) 51 per group 39 ± 23.1 Hosp NR $121,941b
Level II (n = 59) PN 1/21 (5%) 39 per group 36.9 ± 14 Hosp $112,450
Hadfield et al, 199544 ICU (n = 24) EN 2/13 (15%) NR NR NR NR
Level II PN 6/11 (55%)
Baigrie et al, 199645 GI surgery Complications
Level II (n = 97) EN 4/50 (8%) 2/50 (4%) 15/50 (30%)
PN 6/47 (13%) 10/47 (21%) 23/47 (49%)
McClave et al, 199746 Acute EN 0/16 (0%) 2/16 (13%) 9.7 ± 1.3 Hosp NR $761 ± 50.3b
Level II pancreatitis PN 0/16 (0%) 2/16 (13%) 11.9 ± 2.6 Hosp $3294 ± 551.9
(n = 32)
Reynolds et al, 199747 Trauma (n = 67) Complications
Level II EN 2/33 (6%) 10/33 (30%) 11/33 (33%)
PN 1/34 (3%) 19/34 (56%) 6/34 (18%)
Sand et al, 199748 GI surgery Complications
Level II (n = 29) EN 0/13 (0%) 3/13 (23%) 3/13 (23%) Cost of PN was
PN 1/16 (6%) 5/16 (31%) 3/16 (19%) 4 × cost of EN
Kalfarentzos et al, 199722 Acute EN 1/18 (6%) 5/18 (28%)b 40 (25-83) Hosp Savings of 70
Level II pancreatitis PN 2/20 (10%) 10/20 (50%) 39 (22-73) Hosp GBP/d with ENb
(n = 38) Duration MV
EN 11 (5-21) ICU 15 (6-16) d
PN 12 (5-24) ICU 11 (7-31) d
Gianotti et al, 199749 Surgery GI EN 0/87 (0%) 20/87 (23%)c 19.2 ± 7.9 Hosp NR
Level I cancer (n = 176) PN 0/86 (0%) 24/86 (28%) 21.6 ± 8.9 Hosp
Windsor et al, 19988 Acute MOF NR
Level II pancreatitis EN 0/16 (0%) 0/16 (0%) 12.5 (9.5-14) Hosp 0/16 (0%)
(n = 34) PN 2/18 (11%) 3/18 (17%) 15.0 (11-28) Hosp 5/18 (28%)
Woodcock et al, 200150 ICU patients EN 9/17 (53%) 6/16 (38%) 33.2 ± 43 Hosp NR NR
Level II (n = 38) PN 5/21 (24%) 11/21 (52%) 27.3 ± 18.7 Hosp
(continued)
LOS Days, Mean ± SD Other Clinical

Study Population Study Groups ICU Mortality Infectionsa (or Range) Outcomes Cost
Braga et al, 200151 Surgery GI Complications

Level I cancer EN 3/126 (2%) 25/126 (20%) 19.9 ± 8.2 Hosp 45/126 (36%) $25/d
(n = 257) PN 4/131 (3%) 30/131 (23%) 20.7 ± 8.8 Hosp 53/131 (40%) $90/d
Major surgery Postop NR
Pacelli et al, 200152 (n = 241) complications
Level I EN 7/119 (6%) 17/119 (14%) 15.2 ± 3.6 Hosp 45/119 (38%)
PN 3/122 (2%) 14/122 (11%) 16.1 ± 4.5 Hosp 48/122 (39%)
Surgery GI Postop NR
Bozzetti et al, 200153 cancer complications
Level I (n = 317) EN 2/159 (1.3%) 25/159 (16%)b 13.4 ± 4.1 Hospb 54/159 (34%)b
PN 5/158 (3.2%) 42/158 (27%) 15.0 ± 5.6 Hosp 78/158 (49%)
Oláh et al, 200254 Acute pancreatitis MOF NR
Level II (n = 89) EN 2/41 (5%) 5/41 (12%)c 16.8 ± 7.8 Hosp 2/41 (5%)
PN 4/48 (8%) 13/48 (27%) 23.6 ± 10.2 Hosp 5/48 (10%)
Abou-Assi et al, 200255 Acute pancreatitis MOF
Level II (n = 53) EN 8/26 (31%) 5/26 (19%) 14.2 ± 1.9 Hosp 7/26 (27%) $394b
PN 6/27 (22%) 13/27 (48%) 18.4 ± 1.9 Hosp 8/27 (30%) $2756
Gupta et al, 200356 Acute pancreatitis MOF
Level II (n = 17) EN 0/8 (0%) 1/8 (13%) 7 (4-14) Hospb 0/8 (0%) 55 GBP
PN 0/9 (0%) 2/9 (22%) 10 (7-26) Hosp 6/9 (67%) 297 GBP
Louie et al, 200557 Acute pancreatitis MOF
Level II (n = 28) EN 0/10 (0%) 1/10 (10%) 26.2 ± 17.4 Hosp 4/10 (40%) $1375c
PN 3/18 (17%) 5/18 (28%) 40.3 ± 42.4 Hosp 8/18 (44%) $2608
Acute pancreatitis Pancreas MOF NR
Petrov et al, 200658 (n = 70) EN 2/35 (6%) 7/35 (20%)b NR 7/35 (20%)b
Level II PN 12/35 (34%) 16/35 (46%) 17/35 (49%)
Non-pancreas
EN 4/35 (11%)b
PN 11/35 (31%)
Eckerwall et al, 200659 Acute pancreatitis MOF NR
Level II (n = 48) EN 1/23 (4%) 3/23 (13%) 9 (7-14) Hosp 1/23 (4%)
PN 0/25 (0%) 0/25 (0%) 7 (6-14) Hosp 1/25 (4%)
60 Acute pancreatitis MOF NR
Casas et al, 2007
Level II (n = 22) EN 0/11 (0%) 1/11 (9%) 30.2 Hosp 0/11 (0%)
PN 2/11 (18%) 5/11 (45%) 30.7 Hosp 2/11 (18%)
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay; Hosp, hospital; GBP, pounds sterling; MV, mechanical ventilation; neuro, neu-
rologic; MOF, multiple organ failure; GI, gastrointestinal; Postop, postoperative; d, days.
a
b
P ≤ .05.
c
P = .08.
Adapted from the Canadian Clinical Practice Guidelines,21 McClave et al,17 and adapted with permission from Braunschweig et al, Am J Clin Nutr. 2001;74:534-542,
American Society for Nutrition.
283
Table 4. Randomized Studies Evaluating Early Enteral Nutrition (EN) vs Delayed EN in Critically Ill Patients
Ventilator
Study ICU LOS Days, Days,
Study Population Groups Mortality Infectionsa Mean ± SD Mean ± SD Cost
Moore et al, Trauma Early 1/32 (3%) 3/32 (9%) NR NR $16,280 ± 2146
198663 (n = 43) Delayed 2/31 (6%) 9/31 (29%) $19,636 ± 3396
Level II
Chiarelli et al, Burn Early 0/10 (0%) 3/10 (30%)b 69.2 ± 10.4c Hosp NR NR
199064 (n = 20) Delayed 0/10 (0%) 7/10 (70%) 89.0 ± 18.9 Hosp
Level II
Eyer et al, SICU Early 2/19 (11%) 29 per group 11.8 ± 7.9 ICU 10.2 ± 8.1 NR
199365 trauma Delayed 2/19 (11%) 14 per group 9.9 ± 6.7 ICU 8.1 ± 6.8
Level II (n = 52)
Chuntrasakul SICU Early 1/21 (5%) NR 8.1 ± 6.3 ICU 5.29 ± 6.3 NR
et al, 199666 trauma Delayed 3/17 (18%) 8.4 ± 4.8 ICU 6.12 ± 5.3
Level II (n = 38)
Singh et al, Peritonitis Early 4/21 (19%) 7/21 (33%) 14 ± 6.9 Hosp NR NR
199867 (n = 43) Delayed 4/22 (18%) 12/22 (55%) 13 ± 7.0 Hosp
Level II
Minard et al, Closed head Early 1/12 (8%) 6/12 (50%) 30 ± 14.7 Hosp 15.1 ± 7.5 NR
200068 injury Delayed 4/15(27%) 7/15 (47%) 21.3 ± 13.7 Hosp 10.4 ± 6.1
Level II (n = 27) Early 18.5 ± 8.8 ICUc
Delayed 11.3 ± 6.1 ICU
Kompan et al, SICU Early 0/27 (0%) 9/27 (33%) 15.9 ± 9.7 ICU 12.9 ± 8.1 NR
200469 trauma Delayed 1/25 (4%) 16/25 (64%) 20.6 ± 18.5 ICU 15.6 ± 16.1
Level II (n = 52)
Malhotra Postop Early 12/100 (12%) 54/100 (54%) 10.6 Hosp NR NR
et al, 200470 peritonitis Delayed 16/100 (16%) 67/100 (67%) 10.7 Hosp
Level I (n = 200) Early 1.6 ICU
Delayed 2.1 ICU
Peck et al, Burn Early 4/14 (29%) 12/14 (86%) 60 ± 44 Hosp 32 ± 27 NR
200471 (n = 27) Delayed 5/13 (38%) 11/13 (85%) 60 ± 38 Hosp 23 ± 26
Level II Early 40 ±32 ICU
Delayed 37 ± 33 ICU
Dvorak et al, Spinal cord Early 0/7 (0%) 2.4 ± 1.5 per pt 53 ± 34.4 Hosp 31.8 ± 35.0 NR
200472 injury Delayed 0/10 (0%) 1.7 ±1.1 per pt 37.9 ± 14.6 Hosp 20.9 ± 14.4
Level II (n = 17)
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay; Hosp, hospital; SICU, surgical ICU; pt,
patient.
a
b
Bacteremia.
c
P ≤ .05.
Adapted from the Canadian Clinical Practice Guidelines.21
ischemic bowel has been reported most often in the past on stable low doses of pressor agents,76 but any signs of
with use of surgical jejunostomy tubes. However, more intolerance (abdominal distention, increasing nasogastric
recently, this complication has been described with use tube output or gastric residual volumes, decreased passage
of nasojejunal tubes.75 EN intended to be infused into of stool and flatus, hypoactive bowel sounds, increasing
the small bowel should be withheld in patients who are metabolic acidosis and/or base deficit) should be closely
hypotensive (mean arterial blood pressure <60 mm Hg), scrutinized as possible early signs of gut ischemia.
particularly if clinicians are initiating use of catecholamine
agents (eg, norepinephrine, phenylephrine, epinephrine, A6. In the ICU patient population, neither the pres-
dopamine) or escalating the dose of such agents to main- ence nor absence of bowel sounds nor evidence of
tain hemodynamic stability. EN may be provided with passage of flatus and stool is required for the initia-
caution to patients into either the stomach or small bowel tion of enteral feeding. (Grade: B)
Rationale. The literature supports the concept that bowel et al.23 With removal of this study from the meta-analysis,
sounds and evidence of bowel function (ie, passing flatus the difference was no longer significant. The 2 other
or stool) are not required for initiation of enteral feeding. meta-analyses (which did not include the Taylor study)
GI dysfunction in the ICU setting occurs in 30%-70% of showed no difference in pneumonia between gastric and
patients depending on the diagnosis, premorbid condition, post-pyloric feeding.80,81 While 1 showed no difference in
ventilation mode, medications, and metabolic state.77 ICU length of stay,80 all 3 meta-analyses showed no
Proposed mechanisms of ICU and postoperative GI significant difference in mortality between gastric and
dysfunction can be separated into 3 general categories: post-pyloric feeding.80-82 See Table 5.23,68,78,83-91
mucosal barrier disruption, altered motility and atrophy
of the mucosa, and reduced mass of GALT.
B. When to Use Parenteral Nutrition
Bowel sounds are only indicative of contractility and
do not necessarily relate to mucosal integrity, barrier func- B1. If early EN is not feasible or available the first 7
tion, or absorptive capacity. Success at attaining nutrition days following admission to the ICU, no nutrition sup-
goals within the first 72 hours ranges from 30% to 85%. port therapy (ie, STD therapy) should be provided.
When ICU enteral feeding protocols are followed, rates of (Grade: C) In the patient who was previously healthy
GI tolerance in the range of 70%-85% can be achieved.76 prior to critical illness with no evidence of protein-
Ten randomized clinical trials,63-72 the majority in surgical calorie malnutrition, use of PN should be reserved and
critically ill patients, have reported feasibility and safety of initiated only after the first 7 days of hospitalization
enteral feeding within the initial 36-48 hours of admission (when EN is not available). (Grade: E)
to the ICU. The grade of this recommendation is based on
the strength of the literature supporting A3, where patients Rationale. These 2 recommendations are the most con-
in the experimental arm of the above mentioned studies troversial in these guidelines, are influenced primarily by
were successfully started on EN within the first 36 hours 2 meta-analyses, and should be interpreted very carefully
of admission (regardless of clinical signs of stooling, in application to patient care.24,92 Both meta-analyses
flatus, or borborygmi). See Table 4.63-72 compared use of PN with STD therapy (where no nutri-
tion support therapy was provided). In critically ill patients
A7. Either gastric or small bowel feeding is acceptable in the absence of pre-existing malnutrition (when EN is
in the ICU setting. Critically ill patients should be fed not available), Braunschweig et al aggregated 7 studies93-99
via an enteral access tube placed in the small bowel if and showed that use of STD therapy was associated with
at high risk for aspiration or after showing intolerance significantly reduced infectious morbidity (RR = 0.77;
to gastric feeding. (Grade: C) Withholding of enteral 95% CI 0.65-0.91; P <.05) and a trend toward reduced
feeding for repeated high gastric residual volumes overall complications (RR = 0.87; 95% CI 0.74-1.03; P
alone may be sufficient reason to switch to small bowel not provided) compared to use of PN.24 In the same cir-
feeding (the definition for high gastric residual volume cumstances (critically ill, no EN available, and no evi-
is likely to vary from one hospital to the next, as deter- dence of malnutrition), Heyland et al92 aggregated 4
mined by individual institutional protocol). (Grade: E) studies96,97,100,101 and showed a significant increase in
(See guideline D4 for recommendations on gastric mortality with use of PN (RR = 0.1.78; 95% CI 1.11-2.85;
residual volumes, identifying high risk patients, and P < .05) and a trend toward greater rate of complications
reducing chances for aspiration.) (RR = 2.40; 95% CI 0.88-6.58; P not provided), when
compared to STD therapy. See Table 6.93-129
Rationale. Multiple studies have evaluated gastric vs jeju- With increased duration of severe illness, priorities
nal feeding in various medical and surgical ICU settings. between STD therapy and PN become reversed.
One level II study comparing gastric vs jejunal feeding Sandstrom et al first showed that after the first 14 days
showed significantly less gastroesophageal reflux with of hospitalization had elapsed, continuing to provide no
small bowel feeding.78 In a nonrandomized prospective nutrition therapy was associated with significantly greater
study using a radioisotope in an enteral formulation, mortality (21% vs 2%, P < .05) and longer hospital length
esophageal reflux was reduced significantly with a trend of stay (36.3 days vs 23.4 days, P < .05), when compared
toward reduced aspiration as the level of infusion was respectively to use of PN.96 The authors of both meta-
moved from the stomach down through the third portion analyses speculated as to the appropriate length of
of the duodenum.79 Three meta-analyses have been pub- time before initiating PN in a patient on STD therapy
lished comparing gastric with post-pyloric feeding in the who has not begun to eat spontaneously (Braunschweig
ICU setting.80-82 Only 1 of these meta-analyses showed a recommending 7-10 days, Heyland recommending 14
significant reduction in ventilator-associated pneumonia days).24,92 Conflicting data were reported in a Chinese
with post-pyloric feeding (RR = 0.76; 95% CI 0.59-0.99; study of patients with severe acute pancreatitis. In this
P = .04),82 an effect heavily influenced by 1 study by Taylor study, a significant step-wise improvement was seen in
286
Table 5. Randomized Studies Evaluating Small Bowel (SB) vs Gastric Feeding in Critically Ill Patients
Study LOS Days, Mean Nutrition
Study Population Groups ICU Mortality Pneumonia ± SD (or Range) Other Outcomes Outcomes
Montecalvo et al, MICU/SICU (n = 38) Duration MV, % Goal feeds

199283 mean ± SD delivered
Level II SB 5/19 (26%) 4/19 (21%) 11.7 ± 8.2 ICU 10.2 ± 7.1 d 61.0% ± 17.0%
Gastric 5/19 (26%) 6/19 (32%) 12.3 ± 10.8 ICU 11.4 ± 10.8 d 46.9% ± 25.9%
Kortbeek et al, Trauma (n = 80) Duration MV, Time to goal feeds

199984 mean (range)
Level II SB 4/37 (11%) 10/37 (27%) 30 (6-47) Hosp 9 d (2-13 d) 34.0 ± 7.1 h
Gastric 3/43 (7%) 18/43 (42%) 25 (9-88) Hosp 5 d (3-15 d) 43.8 ± 22.6 h
SB 10 (3-24) ICU
Gastric 7 (3-32) ICU
Taylor et al, Trauma head injury NR NR % Goal feeds
199923 (n = 82) delivered
Level II SB 5/41 (12%) 18/41 (44%) 59.2%
Gastric at 6 mo 26/41 (63%) 36.8%
SB 6/41 (15%) 25/41 (61%)a,b
Gastric at 6 mo 35/41 (85%)
Kearns et al, MICU (n = 44) NR % Goal feeds
200085 delivered
Level II SB 5/21 (24%) 4/21 (19%) 39 ± 10 Hosp 69% ± 7%
Gastric 6/23 (26%) 3/23 (13%) 43 ± 11 Hosp 47% ± 7%
SB 17 ± 2 ICU
Gastric 16 ± 2 ICU
Minard et al, Trauma (n = 27) Duration MV, # pts >50% goal ×
200068 mean ± SD 5d
Level II SB 1/12 (8%) 6/12 (50%) 30 ± 14.7 Hosp 15.1 ± 7.5 d 10/12 (83%)
Gastric 4/15 (27%) 7/15 (47%) 21.3 ± 14.7 Hosp 10.4 ± 6.1 d 7/15 (47%)
SB 18.5 ± 8.8 ICUa
Gastric 11.3 ± 6.1 ICU
Lien et al, NR NR NR % Time esophageal NR
200078 Neuro CVA (n = 8) pH <4
Level II SB 12.9 min (4.9-28.2)
Gastric 24.0 min (19.0-40.6)
(continued)
Table 5 (continued)
Study LOS Days, Mean Nutrition
Study Population Groups ICU Mortality Pneumonia ± SD (or Range) Other Outcomes Outcomes
Day et al, 200186 ICU (n = 25) NR NR NR # tubes replaced

Level II SB 0/14 (0%) 16 per group
Gastric 2/11 (18%) 9 per group
Esparza et al, MICU (n = 54) NR NR NR % Goal feeds
200187 delivered
Level II SB 10/27 (37%) 66.0%
Gastric 11/27 (41%) 64.0%
Boivin et al, MICU/SICU/neuro ICU NR NR NR Time to goal feeds
200188 (n = 80) SB 18/39 (46%) 33 h
Level II Gastric 18/39 (46%) 32 h
Neumann et al, MICU (n = 60) NR NR NR Time to goal feeds
200289 SB 1/30 (3%)c 43.0 ± 24.1 h
Level II Gastric 0/30 (0%) 28.8 ± 15.9 h
Davies et al, MICU/SICU (n = 73) NR Time to goal feeds
200290 SB 4/34 (12%) 2/31 (6%) 13.9 ± 1.8 ICUa 23.2 ± 3.9 h
Level II Gastric 5/39 (13%) 1/35 (3%) 10.4 ± 1.2 ICU 23.0 ± 3.4 h
Montejo et al, ICU (n = 101) NR % Goal feeds by

200291 SB 19/50 (38%) 16/50 (32%) 15 ± 10 ICU day 7
Level I Gastric 22/51 (43%) 20/51 (39%) 18 ± 16 ICU 80% ± 28%
75% ± 30%
SD, standard deviation; NR, not reported; ICU, intensive care unit; MICU, medical ICU; SICU, surgical ICU; MV, mechanical ventilation; Pts, patients; CVA, cerebro-
vascular accident; Neuro, neurologic; d, day(s); h, hour(s); min, minute(s); mo, month(s).
a
P ≤ .05.
b
Total infections.
c
Aspiration.
287
Table 6. Randomized Studies Evaluating Parenteral Nutrition (PN) vs Standard Therapy (STD)
288
Protein Energy
Study Population Malnutrition Study Groups Timing of PN Complications Hospital Mortality
Williams et al, 1976102 Esophagogastric Ca (n = 74) PN Preop 2/10 (20%) 6/38 (16%)
Level II STD 7-10 d 3/9 (33%) 8/36 (22%)
Moghissi et al, 1977103 Esophageal Ca (n = 15) PN Preop 0/10 (0%) 0/10 (0%)
Level II STD 5-7 d 1/5 (20%) 0/5 (0%)
Holter et al, 197794 GI Ca (n = 56) 100% PN Preop 4/30 (13%) 2/30 (7%)
Level II STD 3d 5/26 (19%) 2/26 (8%)
Preshaw et al, 1979104 Colon Ca (n = 47) PN Preop 8/24 (33%) 0/24 (0%)
Level II STD 1d 4/23 (17%) 0/23 (0%)
Heatley et al, 1979105 Esophagogastric Ca (n = 74) PN Preop 3/38 (8%)a,b 6/38 (16%)
Level II STD 7-10 d 11/36 (31%) 8/36 (22%)
Simms et al, 1980106 Esophageal Ca (n = 20) PN NR NR 1/10 (10%)
Level II STD 1/10 (10%)
Lim et al, 1981107 Esophageal Ca (n = 20) 100% PN Preop 1/10 (10%) 1/10 (10%)
Level II STD 21 d 4/10 (40%) 2/10 (20%)
Thompson et al, 198198 GI Ca (n = 21) 100% PN Preop 2/12 (17%) 0/12 (0%)
Level II STD 5-14 d 1/9 (11%) 0/9 (0%)
Sako et al, 1981108 Head-neck Ca (n = 66) PN NR 15/30 (50%) 17/34 (50%)
Level II STD 18/32 (56%) 8/32 (25%)
Jensen, 1982109 Rectal Ca (n = 20) 100% PN Preop NR 0/10 (0%)
Level II STD 2d 4/10 (40%)
Moghissi et al, 1982110 Esophageal Ca (n = 52) PN Preop 1/25 (4%) 1/25 (4%)
Level II STD 6-8 d 4/27 (15%) 5/27 (19%)
Muller et al, 198295/1986111 GI Ca (n = 171) 60% PN (gluc) Preop 11/66 (17%)b 3/66 (5%)b
Level I PN (gluc/lipid) 10 d 17/46 (37%) 10/46 (22%)
STD 19/59 (32%) 11/59 (19%)
Garden et al, 1983112 Perioperative (n = 20) PN NR 1/10 (10%) 0/10 (0%)
Level II STD 2/10 (20%) 1/10 (10%)
Sax et al, 198797 Acute pancreatitis (n = 55) 0% PN NA 4/29 (14%)c 1/29 (3%)
Level II STD 1/26 (4%) 1/26 (4%)
Bellantone et al, 1988113 GI Ca (n = 91) 100% PN Preop 12/40 (30%)c 1/40 (3%)
(JPEN) Level II STD ≥7 d 18/51 (35%) 2/51 (4%)
Smith et al, 1988114 GI Ca (n = 34) 100% PN Preop 3/17 (18%) 1/17 (6%)
Level II STD 8-15 d 6/17 (35%) 3/17 (18%)
Meguid et al, 1988115 GI Ca (n = 66) 100% PN Preop 10/32 (31%)b 1/32 (3%)
Level II STD 8d 19/34 (56%) 0/34 (0%)
Bellantone et al, 1988116 GI Ca (n = 100) PN Preop 8/54 (15%)b,c 1/54 (2%)
Level I STD ≥7 d 22/46 (48%) 1/46 (2%)
Fan et al, 1989117 Esophageal Ca (n = 40) 75% PN Preop 17/20 (85%) 6/20 (30%)
Level II STD 14 d 15/20 (75%) 6/20 (30%)
VA Co-OP 1991118 Perioperative (n = 459) 100% PN Preop 49/192 (26%) 31/231 (13%)
Level I STD 7-15 d 50/203 (25%) 24/228 (11%)
(continued)
Protein Energy
Study Population Malnutrition Study Groups Timing of PN Complications Hospital Mortality
Von Meyenfeldt et al, 1992119 Perioperative (n = 101) 29% PN Preop 6/51 (12%) 2/51 (4%)
Level I STD 10-23 d 7/50 (14%) 2/50 (4%)
Fan et al, 1994120 Hepatocellular Ca (n = 124) 26% PN Preop 22/64 (34%)b 5/64 (8%)
Level I STD 7d 33/60 (55%) 9/60 (15%)
Xian-Li et al, 2004121 Acute pancreatitis (n = 44) PN NA 11/21 (52%)c 3/21 (14%)
Level II STD 21/23 (91%) 10/23 (44%)
Abel et al, 1976100 Perioperative (n = 44) 100% PN Postop 2/20 (10%) 4/20 (20%)
Level II STD 0/24 (0%) 3/24 (13%)
Collins et al, 1978122 GI surgery (n = 20) 40% PN Postop 2/10 (20%) 0/10 (0%)
Level II STD 0/10 (0%) 0/10 (0%)
Freund et al, 1979123 GI surgery (n = 35) 0% PN Postop 0/25 (0%) 0/25 (0%)
Level II STD 0/10 (0%) 0/10 (0%)
Yamada et al, 1983124 GI surgery (n = 57) PN Postop 0/29 (0%) 0/29 (0%)
Level II STD 5/28 (18%) 1/28 (4%)
Jiménez et al, 1986125 GI surgery (n = 75) 100% PN Postop 6/60 (10%) 4/60 (7%)
Level II STD 3/15 (20%) 1/15 (7%)
Askanazi et al, 1986126 GU surgery (n = 35) PN Postop 1/22 (5%) 0/22 (0%)
Level II STD 2/13 (15%) 2/13 (15%)
Figueras et al, 1988127 GI surgery (n = 49) 0% PN Postop 4/25 (16%) 0/25 (0%)
Level II STD 5/24 (21%) 0/24 (0%)
Woolfson et al, 198999 Perioperative (n = 122) 0% PN Postop 6/62 (10%) 8/62 (13%)
Level I STD 4/60 (7%) 8/60 (13%)
Reilly et al, 1996101 Liver transplant (n = 28) 100% PN Postop NR 0/8 (0%)
Level II PN/BCAA 1/10 (10%)
STD 2/10 (20%)
Gys et al, 1990128 GI surgery (n = 20) 0% PN Postop 1/10 (10%) 0/10 (0%)
Level II STD 1/10 (10%) 0/10 (0%)
Sandstrom et al, 199396 Surgery, trauma (n = 300) 23% PN Postop NR 12/150 (8%)
Level I STD 10/150 (7%)
Hwang et al, 1993129 GI surgery (n = 58) PN Postop 0/26 (0%) 0/26 (0%)
Level II STD 0/32 (0%) 0/32 (0%)
Brennan et al, 199493 Pancreatic Ca (n = 117) 100% PN Postop 27/60 (45%) 4/60 (7%)
Level I STD 13/57 (23%) 1/57 (2%)
Ca, cancer; GI, gastrointestinal; NA, not applicable; NR, not reported; BCAA, branch chain amino acids; Postop, postoperative; gluc, glucose; Preop, preoperative;
d, day(s).
a
wound infection.
b
P < .05.
c
Infection.
Adapted from Heyland et al,21 Klein et al,131 and with permission from Braunschweig et al, Am J Clin Nutr. 2001;74:534-542, American Society for Nutrition and
289
Detsky et al, Ann Intern Med. 1987;107:195-203,130 American College of Physicians.
each clinical outcome parameter (hospital length of stay, only if the duration of therapy is antici-
pancreatic infection, overall complications, and mortal- pated to be ≥7 days. (Grade: B)
ity) when comparing patients randomized to STD therapy
vs PN vs PN with parenteral glutamine, respectively.121 Rationale. One population of patients that has shown
Because of the discrepancy, we attempted to contact the more consistent benefit of PN over STD involve those
authors of this latter study to get validation of results patients undergoing major upper GI surgery (esophagec-
but were unsuccessful. The final recommendation was tomy, gastrectomy, pancreatectomy, or other major reop-
based on the overall negative treatment effect of PN over erative abdominal procedures), especially if there is
the first week of hospitalization seen in the 2 meta- evidence of preexisting protein-calorie malnutrition and
analyses.24,92 Although the literature cited recommends the PN is provided under specific conditions.24,92 Whereas
withholding PN for 10-14 days, the Guidelines Committee critically ill patients in the Heyland meta-analysis experi-
expressed concern that continuing to provide STD ther- enced increased mortality with use of PN compared to
apy (no nutrition support therapy) beyond 7 days would STD therapy (see rationale for guideline B1 above), surgi-
lead to deterioration of nutrition status and an adverse cal patients saw no treatment effect with PN regarding
effect on clinical outcome. mortality (RR = 0.91; 95% CI 0.68-1.21; P = NS).92
Critically ill patients experienced a trend toward increased
B2. If there is evidence of protein-calorie malnutri- complications, while surgical patients saw significant
tion on admission and EN is not feasible, it is appro- reductions in complications with use of PN regarding
priate to initiate PN as soon as possible following mortality (RR = 2.40; 95% CI 0.88-6.58; P < .05).92
admission and adequate resuscitation. (Grade: C) These benefits were noted when PN was provided
preoperatively for a minimum of 7-10 days and then
Rationale. In the situation where EN is not available and continued through the perioperative period. In an ear-
evidence of protein-calorie malnutrition is present (usu- lier meta-analysis by Detsky et al130 comparing periop-
ally defined by recent weight loss of >10%-15% or actual erative PN with STD therapy, only seven95,98,102,103,107,110,111
body weight <90% of ideal body weight), initial priorities out of 14 studies94,100,104,106,108,109,112 provided PN for ≥7
are reversed and use of PN has a more favorable outcome days.130 As a result, only 1 study showed a treatment
than STD therapy. See Table 6.93-129 effect95 and the overall meta-analysis showed no statisti-
In the Heyland meta-analysis, use of PN in mal- cally significant benefit from PN.130 In contrast, a later
nourished ICU patients was associated with significantly meta-analysis by Klein et al131 aggregated the data from
fewer overall complications (RR = 0.52; 95% CI 0.30- 13 studies,95,98,103,105,111,113-120 all of which provided PN
0.91; P < .05) than STD therapy.92 In the Braunschweig for ≥7 days.131 Six of the studies showed significant ben-
meta-analysis, STD therapy in malnourished ICU eficial treatment effects from use of PN,95,103,105,111,115,120
patients was associated with significantly higher risk for with the pooled data from the overall meta-analysis
mortality (RR = 3.0; 95% CI 1.09-8.56; P < .05) and a showing a significant 10% decrease in infectious mor-
trend toward higher rate of infection (RR = 1.17; 95% bidity compared to STD therapy.131 See Table 6.93-129
CI 0.88-1.56; P not provided) compared to use of PN.24 It is imperative to be aware that the beneficial effect
For these patients, when EN is not available, there of PN is lost if given only postoperatively. Aggregation of
should be little delay in initiating PN after admission to data from 9 studies that evaluated routine postoperative
the ICU. PN93,94,96,99-101,104,109,122 showed a significant 10% increase
in complications compared to STD therapy.131 Because of
B3. If a patient is expected to undergo major upper the adverse outcome effect from PN initiated in the
GI surgery and EN is not feasible, PN should be pro- immediate postoperative period, Klein et al recommended
vided under very specific conditions: delaying PN for 5-10 days following surgery if EN contin-
If the patient is malnourished, PN should ues not to be feasible.131
be initiated 5-7 days preoperatively and
continued into the postoperative period.
C. Dosing of Enteral Feeding
(Grade: B)
PN should not be initiated in the immediate C1. The target goal of EN (defined by energy require-
postoperative period but should be delayed ments) should be determined and clearly identified at
for 5-7 days (should EN continue not to be the time of initiation of nutrition support therapy.
feasible). (Grade: B) (Grade: C) Energy requirements may be calculated
PN therapy provided for a duration of <5-7 by predictive equations or measured by indirect calo-
days would be expected to have no outcome rimetry. Predictive equations should be used with
effect and may result in increased risk to caution, as they provide a less accurate measure of
the patient. Thus, PN should be initiated energy requirements than indirect calorimetry in the
individual patient. In the obese patient, the predic- immunity. In patients already receiving some volume of EN,
tive equations are even more problematic without use of supplemental PN over the first 7-10 days adds
availability of indirect calorimetry. (Grade: E) cost137,138 and appears to provide no additional benefit.42,137-140
In 1 small study in burn patients, EN supplemented with
Rationale. Clinicians should clearly identify the goal of PN was associated with a significant increase in mortality
EN, as determined by energy requirements. Over 200 pre- (63% vs 26%, P < .05) when compared respectively to
dictive equations (including Harris-Benedict, Scholfield, hypocaloric EN alone.138 See Table 7.42,137-140
Ireton-Jones, etc) have been published in the literature.132 As discussed in guideline B1, the optimal time to
Energy requirements may be calculated either through initiate PN in a patient who is already receiving some
simplistic formulas (25-30 kcal/kg/d), published predictive volume of enteral feeding is not clear. The reports by
equations, or the use of indirect calorimetry. Calories pro- Braunschweig et al and Sandstrom et al infer that after
vided via infusion of propofol should be considered when the first 7-10 days, the need to provide adequate calories
calculating the nutrition regimen. While it is often diffi- and protein is increased in order to prevent the conse-
cult to provide 100% of goal calories by the enteral route, quences of deterioration of nutrition status.24,96 At this
studies in which a protocol was used to increase delivery point, if the provision of EN is insufficient to meet
of EN have shown that delivering a volume of EN where requirements, then the addition of supplemental PN
the level of calories and protein provided is closer to goal should be considered.
improves outcome.133,134 This recommendation is sup-
ported by two level II studies in which those patients who C4. Ongoing assessment of adequacy of protein provi-
by protocol randomization received a greater volume of sion should be performed. The use of additional
EN experienced significantly fewer complications and less modular protein supplements is a common practice,
infectious morbidity,23 as well as shorter hospital lengths as standard enteral formulations tend to have a high
of stay, and a trend toward lower mortality135 than those non-protein calorie:nitrogen ratio. In patients with
patients receiving lower volume. body mass index (BMI) <30, protein requirements
should be in the range of 1.2-2.0 g/kg actual body
C2. Efforts to provide >50%-65% of goal calories should weight per day, and may likely be even higher in burn
be made in order to achieve the clinical benefit of EN or multi-trauma patients. (Grade: E)
over the first week of hospitalization. (Grade: C)
Rationale. In the critical care setting, protein appears to
Rationale. The impact of early EN on patient outcome be the most important macronutrient for healing wounds,
appears to be a dose-dependent effect. “Trickle” or trophic supporting immune function, and maintaining lean body
feeds (usually defined as 10-30 mL/h) may be sufficient mass. For most critically ill patients, protein requirements
to prevent mucosal atrophy but may be insufficient to are proportionately higher than energy requirements and
achieve the usual endpoints desired from EN therapy. therefore are not met by provision of routine enteral for-
Studies suggest that >50%-65% of goal calories may be mulations. The decision to add protein modules should
required to prevent increases in intestinal permeability in be based on an ongoing assessment of adequacy of pro-
burn and bone-marrow transplant patients, to promote tein provision. Unfortunately in the critical care setting,
faster return of cognitive function in head injury patients, determination of protein requirements is difficult but
and to improve outcome from immune-modulating enteral may be derived with limitations from nitrogen balance,
formulations in critically ill patients.5,23,133,136 This recom- simplistic equations (1.2-2.0 g/kg/d) or non-protein
mendation is supported by one level II23 and one level III calorie:nitrogen ratio (70:1-100:1). Serum protein mark-
study136 where increases in the percent goal calories ers (albumin, prealbumin, transferrin, C-reactive protein)
infused from a range of 37%-40% up to 59%-64% improved are not validated for determining adequacy of protein
clinical outcome. provision and should not be used in the critical care set-
ting in this manner.141
C3. If unable to meet energy requirements (100% of
target goal calories) after 7-10 days by the enteral C5. In the critically ill obese patient, permissive
route alone, consider initiating supplemental PN. underfeeding or hypocaloric feeding with EN is rec-
(Grade: E) Initiating supplemental PN prior to this ommended. For all classes of obesity where BMI is
7-10 day period in the patient already receiving EN >30, the goal of the EN regimen should not exceed
does not improve outcome and may be detrimental to 60%-70% of target energy requirements or 11-14 kcal/
the patient. (Grade: C) kg actual body weight per day (or 22-25 kcal/kg ideal
body weight per day). Protein should be provided in a
Rationale. Early on, EN is directed toward maintaining gut range ≥2.0 g/kg ideal body weight per day for Class I
integrity, reducing oxidative stress, and modulating systemic and II patients (BMI 30-40), ≥2.5 g/kg ideal body
Table 7. Randomized Studies Evaluating Enteral Nutrition (EN) vs EN Supplemented

With Parenteral Nutrition (EN+PN) in Critically Ill Patients
Ventilator
Study LOS Day(s), Days, Mean
Study Population Groups Mortality Infections Mean ± SD ± SD Cost
Herndon et al, Burn EN+PN 8/13 (62%) ICU NR NR NR NR

1987139 (n = 28) EN 8/15 (53%) ICU
Level II
Herndon et al, Burn EN+PN 10/16 (63%) > 14 da NR NR NR NR
1989140 (n = 39) EN 6/23 (26%) > 14 d
Level II
Dunham et al, Trauma EN+PN 3/10 (30%) ICU NR NR NR NR
199442 (n = 37) EN 1/12 (8%) ICU
Level II
Chiarelli et al, ICU EN+PN 3/12 (25%) ICU 6/12 (50%) 37 ± 13 Hosp 19 ± 6 EN+PN 50,000a
1996137 (n = 24) EN 4/12 (33%) ICU 3/12 (25%) 41 ± 23 Hosp 19 ± 2 lira/yr more
Level II than EN
Bauer et al, ICU EN+PN 3/60 (5%) at 4 d 39/60 (65%) 31.2 ± 18.5 Hosp 11 ± 9 204 ± 119
2000138 (n = 120) EN 4/60 (7%) at 4 d 39/60 (65%) 33.7 ± 27.7 Hosp 10 ± 8 Euros/pta
Level I EN+PN 17/60 (28%) at 90 d 16.9 ± 11.8 ICU 106 ± 47
EN 18/60 (30%) at 90 d 17.3 ± 12.8 ICU Euros/pt
SD, standard deviation; NR, not reported; ICU, intensive care unit; Hosp, hospital; LOS, length of stay; pt, patient; d, day(s); yr, year(s)
a
P ≤ .05.
weight per day for Class III (BMI ≥ 40). Determining bowel sounds or the passage of flatus and stool. EN pro-
energy requirements is discussed in guideline C1. motes gut motility. As long as the patient remains hemo-
(Grade: D) dynamically stable, it is safe and appropriate to feed
through mild to moderate ileus.2
Rationale. Severe obesity adversely affects patient care in
the ICU and increases risk of comorbidities (eg, insulin D2. Patients should be monitored for tolerance of
resistance, sepsis, infections, deep venous thrombosis, EN (determined by patient complaints of pain and/
organ failure).142,143 Achieving some degree of weight loss or distention, physical exam, passage of flatus and
may increase insulin sensitivity, improve nursing care, stool, abdominal radiographs). (Grade: E)
and reduce risk of comorbidities. Providing 60%-70% of Inappropriate cessation of EN should be avoided.
caloric requirements promotes steady weight loss, while (Grade: E) Holding EN for gastric residual volumes
infusing protein at a dose of 2.0-2.5 g/kg ideal body <500 mL in the absence of other signs of intoler-
weight per day should approximate protein requirements ance should be avoided. (Grade: B) The time period
and neutral nitrogen balance, allowing for adequate that a patient is made nil per os (NPO) prior to,
wound healing.142 A retrospective study by Choban and during, and immediately following the time of diag-
Dickerson indicated that provision of protein at a dose of nostic tests or procedures should be minimized to
2.0 g/kg ideal body weight per day is insufficient for prevent inadequate delivery of nutrients and pro-
achieving neutral nitrogen balance when the BMI is longed periods of ileus. Ileus may be propagated by
>40.142 Use of BMI and ideal body weight is recom- NPO status. (Grade: C)
mended over use of adjusted body weight.
Rationale. A number of factors impede the delivery of EN
D. Monitoring Tolerance and Adequacy in the critical care setting.144 Healthcare providers who
prescribe nutrition formulations tend to under-order calo-
of Enteral Nutrition
ries, and thus patients only receive approximately 80% of
D1. In the ICU setting, evidence of bowel motility what is ordered. This combination of under-ordering and
(resolution of clinical ileus) is not required in order to inadequate delivery results in patients receiving only 50%
initiate EN in the ICU. (Grade: E) of target goal calories from one day to the next. Cessation
of feeding occurs in >85% of patients for an average of
Rationale. Feeding into the GI tract is safe prior to the 20% of the infusion time (the reasons for which are avoid-
emergence of overt evidence of enteric function, such as able in >65% of occasions).144 Patient intolerance accounts
Table 8. Randomized Studies Evaluating Lower vs Higher “Cutoff Values” for Gastric Residual Volumes (GRVs)
% Goal kcal
Study Groups Infused Aspiration GI Intolerance
Study Population by GRVsa Mean ± SD Pneumonia Mean ± SD Mean ± SD Other
Taylor et al, 199923 Trauma, head NR NR Infection
Level II injury (n = 82) 150/50 mLb 36% 26/41 (63%) 35/41 (85%)
200 mL 59%c 18/41 (44%) 25/41 (61%)c
Complications
150/50 mL 25/41 (61%)
200 mL 15/41 (37%)c
Hospital LOS
150/50 mL 46 d
200 mL 30 dc
Pinilla et al, 2001146 ICU (n = 80) NR ICU LOS
Level II 150 mL 70% ± 25% 0/36 (0%) 21/36 (58%) 13.2 ± 18.3 d
250 mL 76% ± 18% 1/44 (2%) 20/44 (45%) 9.5 ± 9.4 d
McClave et al, ICU (n = 40) 200 mL 77.0% ± 21.2% NR 21.6% ± 25.6%d 35.0% ± 27.3%e
2005151 400 mL 77.8% ± 32.5% 22.6% ± 25.0% 27.8% ± 25.0%
Level II
ICU (n = 329) 200 mL 82.8% ± 1.7%f 46/169 (27%) NR 107/169 (64%)
Montejo et al, 2008147 500 mL 89.6% ± 1.8%c 45/160 (28%) 76/160 (48%)c
Level I
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay; GI, gastrointestinal; d, day(s).
a
Cutoff value of volume above which there is automatic cessation of EN.
b
EN advanced if GRVs <50 mL, automatic cessation if >150 mL.
c
P ≤ .05.
d
Incidence of aspiration as a percentage of all bedside checks done every 4 hours.
e
Incidence of regurgitation as a percentage of all bedside checks done every 4 hours.
f
Percentage goal feeding on day 3 (similar to significant differences on day 7).
for one-third of cessation time, but only half of this rep- of measures to reduce risk of aspiration, but automatic
resents true intolerance. Other reasons for cessation cessation of feeding should not occur for gastric residual
include remaining NPO after midnight for diagnostic volumes <500 mL in the absence of other signs of intol-
tests and procedures in another third of patients, with the erance.152 See Table 8.23,146,147,151
rest being accounted for by elevated gastric residual
volumes and tube displacement.144 In one level II D3. Use of enteral feeding protocols increases the
study, patients randomized to continue EN during fre- overall percentage of goal calories provided and should
quent surgical procedures (burn wound debridement be implemented. (Grade: C)
under general anesthesia) had significantly fewer infec-
tions than those patients for whom EN was stopped for Rationale. Use of ICU or nurse-driven protocols which
each procedure.145 define goal infusion rate, designate more rapid startups,
Gastric residual volumes do not correlate well to and provide specific orders for handling gastric residual
incidence of pneumonia,23,146,147 measures of gastric volumes, frequency of flushes, and conditions or prob-
emptying,148-150 or to incidence of regurgitation and aspi- lems under which feeding may be adjusted or stopped,
ration.151 Four level II studies indicate that raising the have been shown to be successful in increasing the over-
cutoff value for gastric residual volume (leading to auto- all percentage of goal calories provided.23,76,133,135,153,154
matic cessation of EN) from a lower number of 50-150
mL to a higher number of 250-500 mL does not increase D4. Patients placed on EN should be assessed for risk
risk for regurgitation, aspiration, or pneumonia.23,146,147,151 of aspiration. (Grade: E) Steps to reduce risk of aspi-
Decreasing the cutoff value for gastric residual volume ration should be employed. (Grade: E)
does not protect the patient from these complications, The following measures have been shown to reduce
often leads to inappropriate cessation, and may adversely risk of aspiration:
affect outcome through reduced volume of EN infused.23 In all intubated ICU patients receiving EN,
Gastric residual volumes in the range of 200-500 mL the head of the bed should be elevated
should raise concern and lead to the implementation 30°-45°. (Grade: C)
Table 9. Randomized Studies Evaluating Body Position During Tube Feeding

in Critically Ill Patients, Supine vs Semirecumbent
Ventilator
Hospital LOS Days, Mean
Days, Mean ± ± SD (or
Study Population Study Groups Mortality Pneumonia SD (or Range) Range)
Drakulovic et al, 1999158 ICU (n = 90) Semi-rec 7/39 (18%) ICU 2/39 (5%)a 9.7 ± 7.8 ICU 7.1 ± 6.9
Level II Supine 13/47 (28%) ICU 11/47 (23%) 9.3 ± 7.2 ICU 6.0 ± 6.2
van Nieuwenhoven ICU (n = 221) Semi-rec 33/112 (29%) ICU 13/112 (12%) 27 (2-301) Hosp 6 (0-64)
et al, 2006159 Supine 33/109 (30%) ICU 8/109 (7%) 24 (0-186) Hosp 6 (0-281)
Level I Semi-rec 44/112 (39%) Hosp 9 (0-281) ICU
Supine 41/109 (38%) Hosp 10 (9-91) ICU
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay; Hosp, hospital; Semi-rec, semi-reclined.
a
P ≤ .05.
For high-risk patients or those shown to be Elevating the head of the bed 30°-45° was shown in
intolerant to gastric feeding, delivery of EN 1 study to reduce the incidence of pneumonia from 23%
should be switched to continuous infusion. to 5%, comparing supine to semi-recumbent position,
(Grade: D) respectively (P = .018).158 See Table 9.158,159
Agents to promote motility such as prokinetic The potential harm from aggressive bolus infusion of
drugs (metoclopramide and erythromycin) EN leading to increased risk of aspiration pneumonia
or narcotic antagonists (naloxone and alvi- was shown in 1 study.160 Level II studies comparing
mopan) should be initiated where clinically bolus to continuous infusion have shown greater
feasible. (Grade: C) volume with fewer interruptions in delivery of EN with
Diverting the level of feeding by post-pyloric continuous feeding but no significant difference between
tube placement should be considered. techniques with regard to patient outcome.161,162 See
(Grade: C) Table 10.161-165
Use of chlorhexidine mouthwash twice a day should Adding prokinetic agents such as erythromycin or
be considered to reduce risk of ventilator-associated metoclopramide has been shown to improve gastric
pneumonia. (Grade: C) emptying and tolerance of EN but has resulted in
little change in clinical outcome for ICU patients.166 See
Rationale. Aspiration is one of the most feared complica- Table 11.167-169 Use of naloxone infused through the feed-
tions of EN. Patients at increased risk for aspiration may ing tube (to reverse the effects of opioid narcotics at the
be identified by a number of factors, including use of a level of the gut in order to improve intestinal motility) was
nasoenteric tube, an endotracheal tube and mechanical shown in one level II study to significantly increase the
ventilation, age >70 years, reduced level of conscious- volume of EN infused, reduce gastric residual volumes,
ness, poor nursing care, location in the hospital, patient and decrease the incidence of ventilator-associated pneu-
position, transport out of the ICU, poor oral health, and monia (compared to placebo).169
use of bolus intermittent feedings.152 Pneumonia and Optimizing oral health with chlorhexidine mouth-
bacterial colonization of the upper respiratory tree are washes twice daily was shown in 2 studies to reduce respi-
more closely associated with aspiration of contaminated ratory infection and nosocomial pneumonia in patients
oropharyngeal secretions than regurgitation and aspira- undergoing heart surgery.170,171 While studies evaluating
tion of contaminated gastric contents.155-157 use of chlorhexidine in general ICU populations have
Several methods may be used to reduce the risk of shown little outcome effect, 2 studies in which chlorhexi-
aspiration. As mentioned in guideline A6, changing the dine oral care was included in bundled interventions
level of infusion of EN from the stomach to the small showed significant reductions in nosocomial respiratory
bowel has been shown to reduce the incidence of regur- infections.172,173 Other steps to decrease aspiration risk
gitation and aspiration,78,79 although the results from 3 would include reducing the level of sedation/analgesia
meta-analyses (as discussed under guideline A6) suggest when possible, minimizing transport out of the ICU for
that any effect in reducing pneumonia is minimal.80-82 diagnostic tests and procedures, and moving the patient to
See Table 5.23,68,78,83-91 a unit with a lower patient:nurse ratio.152,174
Table 10. Randomized Studies Evaluating Continuous vs Bolus Delivery of Enteral Nutrition (EN)
ICU
Study Population Study Groups Infection Difference in Feeding Mortality Other
Hiebert et al, NR Time to goal calories Diarrhea (stool frequency)

1981163 Burn (n = 76) Continuous 3.1 ± 0.7 da 1.8 ± 0.4a
Level II Bolus 5.2 ± 0.8 d 3.3 ± 0.7
Kocan et al, Neuro ICU NR % Goal calories infused NR Aspiration (blue food coloring)
1986164 (n = 34) Continuous 62.2% 1/17 (6%)
Level II Bolus 55.9% 3/17 (18%)
Ciocon et al, Hospitalized Daily caloric deficit NR Clogged tube
1992165 dysphagia Continuous 5/30 (17%)b 783 ± 29 kcal/d 15/30 (50%)a
Level II (n = 60) Bolus 10/30 (33%) 795 ± 25 kcal/d 5/30 (17%)
Diarrhea
Continuous 20/30 (67%)a
Bolus 29/30 (97%)
Bonten et al, ICU (n = 60) Interrupted EN Mortality
1996161 Continuous 5/30 (17%) 2/30 (7%) 6/30 (20%) 6/30 (20%)
Level II Bolusc 5/30 (17%) 5/30 (17%) 9/30 (30%) 9/30 (30%)
Steevens et al, Trauma ICU Interrupted EN NR
2002162 (n = 18) Continuous 0/9 (0%)b 3/9 (33%)
Level II Bolus 1/9 (11%) 5/9 (56%)
SD, standard deviation; NR, not reported; ICU, intensive care unit; Neuro, neurologic; d, day(s).
a
P ≤ .05.
b
Aspiration.
c
Intermittent feeding.
Table 11. Randomized Studies With vs Without Motility Agents in Critically Ill Patients
Study Population Study Groups ICU Mortality Pneumonia Nutrition Outcomes
Yavagal et al, ICU (n = 305) Metoclopramide 10 mg NG 73/ 131 (56%) 22/131 (17%) NR
2000167 Placebo 92/174 (53%) 24/174 (14%)
Level I
Berne et al, Trauma (n = 48) EN tolerated at 48 h
2002168 Erythromycin 250 mg IV q 6 h 2/32 (6%) 13/32 (40%) 58%
Level II Placebo 2/36 (6%) 18/36 (50%) 44%
EN tolerated during study
Erythromycin 250 mg IV q 6 h 65%
Placebo 59%
Meissner et al, ICU (n = 84) Mean GRV
2003169 Naloxone 8 mg q 6 h NG 6/38 (16%) 13/38 (34%)a 54 mL
Level II Placebo 7/43 (16%) 24/43 (56%) 129 mL
Volume EN delivered was higher
after day 3 in Naloxone group
compared to controls (trend)
NR, not reported; ICU, intensive care unit; GRV, gastric residual volume; IV, intravenous; NG, nasogastric; EN, enteral nutrition;
h, hour(s).
a
P ≤ .05.
D5. Blue food coloring and glucose oxidase strips, as toxicity and patient death.175 The United States Food and
surrogate markers for aspiration, should not be used Drug Administration through a Health Advisory Bulletin
in the critical care setting. (Grade: E) (September 2003) issued a mandate against the use of
blue food coloring as a monitor for aspiration in patients
Rationale. Traditional monitors for aspiration are ineffec- on EN.176 The basic premise for use of glucose oxidase
tive. Blue food coloring, an insensitive marker for aspira- (that glucose content in tracheal secretions is solely
tion, was shown to be associated with mitochondrial related to aspiration of glucose-containing formulation)
has been shown to be invalid, and its use is thwarted by These myeloid suppressor cells are capable of causing
poor sensitivity/specificity characteristics.177 states of severe arginine deficiency which impact produc-
tion of nitric oxide and negatively affect microcirculation.
D6. Development of diarrhea associated with enteral Immune-modulating diets containing arginine and ω-3
tube feedings warrants further evaluation for etiology. fatty acids appear to overcome the regulatory effect of
(Grade: E) myeloid suppressor cells.205 Agents such as RNA nucle-
otides increase total lymphocyte count, lymphocyte pro-
Rationale. Diarrhea in the ICU patient receiving EN should liferation, and thymus function. In a dynamic fashion, the
prompt an investigation for excessive intake of hyperos- ω-3 fatty acids eicosapentaenoic acid (EPA) and docoso-
molar medications, such as sorbitol, use of broad spec- hexaenoic acid (DHA) displace ω-6 fatty acids from the
trum antibiotics, Clostridium difficile pseudomembranous cell membranes of immune cells. This effect reduces
colitis, or other infectious etiologies. Most episodes of systemic inflammation through the production of alterna-
nosocomial diarrhea are mild and self-limiting.178 tive biologically less active prostaglandins and leukot-
Assessment should include an abdominal exam, fecal rienes. EPA and DHA (fish oils) have also been shown
leukocytes, quantification of stool, stool culture for C. to down-regulate expression of nuclear factor-kappa B
difficile (and/or toxin assay), serum electrolyte panel (to (NFkB), intracellular adhesion molecule 1 (ICAM-1), and
evaluate for excessive electrolyte losses or dehydration), E-selectin, which in effect decreases neutrophil attach-
and review of medications. An attempt should be made to ment and transepithelial migration to modulate systemic
distinguish infectious diarrhea from osmotic diarrhea.179 and local inflammation. In addition, EPA and DHA help
to stabilize the myocardium and lower the incidence
E. Selection of Appropriate Enteral Formulation of cardiac arrhythmias, decrease incidence of acute respi-
ratory distress syndrome (ARDS), and reduce the likeli-
E1. Immune-modulating enteral formulations (sup- hood of sepsis.206-209 Glutamine, considered a conditionally
plemented with agents such as arginine, glutamine, essential amino acid, exerts a myriad of beneficial effects
nucleic acid, ω-3 fatty acids, and antioxidants) should on antioxidant defenses, immune function, production of
be used for the appropriate patient population (major heat shock proteins, and nitrogen retention. Addition of
elective surgery, trauma, burns, head and neck cancer, agents such as selenium, ascorbic acid (vitamin C), and
and critically ill patients on mechanical ventilation), vitamin E provides further antioxidant protection.
with caution in patients with severe sepsis. Multiple meta-analyses181,182,210-212 have shown that
(For surgical ICU patients, Grade: A) use of immune-modulating formulations is associated
(For medical ICU patients, Grade: B) with significant reductions in duration of mechanical
ICU patients not meeting criteria for immune-modu- ventilation, infectious morbidity, and hospital length of
lating formulations should receive standard enteral stay compared to use of standard enteral formulations.
formulations. (Grade: B) These same 5 meta-analyses showed no overall impact
on mortality from use of immune-modulating formula-
Rationale. In selecting the appropriate enteral formulations. See Table 13.181,182,210-212 The beneficial outcome
tion for the critically ill patient, the clinician must first effects of the immune-modulating formulations are more
decide if the patient is a candidate for a specialty immune- uniformly seen in patients undergoing major surgery
modulating formulation.180 Patients most likely to show than in critically ill patients on mechanical ventilation.
a favorable outcome, who thus would be appropriate This influence is even more pronounced when the for-
candidates for use of immune-modulating formulations, mulation is given in the preoperative period. By differen-
include those undergoing major elective GI surgery, tiating studies done in surgical ICUs from those done in
trauma (abdominal trauma index scores >20), burns (total medical ICUs, Heyland et al showed that the greatest
body surface area >30%), head and neck cancer, and beneficial effect was seen in surgery patients with sig-
critically ill patients on mechanical ventilation (who are nificant reductions in infectious morbidity (RR = 0.53;
not severely septic).180 95% CI 0.42-0.68; P ≤ .05) and hospital length of stay
A large body of data suggest that adding pharmaconu- (WMD = –0.76; 95% CI –1.14 to –0.37; P < .05). 210 In
trients to enteral formulations provides even further contrast, aggregating the data from studies in medical
benefits on patient outcome than use of standard formu- ICU patients showed no effect on infections (RR = 0.96;
lations alone.181-183 See Table 12.184-204 Studies from basic 95% CI 0.77-1.20; P = NS) but a similar reduction in
science have provided a rationale for the mechanism hospital length of stay (WMD = –0.47; 95% CI –0.93 to
of the beneficial effects seen clinically. Such findings –0.01; P = .047).210
include the discovery of specialized immune (myeloid It has been hypothesized that there may be some
suppressor) cells, whose role is to regulate the availability increased risk with the use of arginine-containing formu-
of arginine, necessary for normal T lymphocyte function. lations in medical ICU patients who are severely
Table 12. Immune-Modulating Enteral Nutrition (EN) vs Standard EN (Stand EN) in Critically Ill Patients
LOS Days, Ventilator Days, Mean
Study Population Study Groups Mortality Infectionsa Mean ± SD (or Range) ± SD (or Range)
Cerra et al, 1990184 Surgical ICU Impactb 1/11 (9%) ICU NR 36.7 ± 8.5 Hospc NR
Level II (n = 20) Osmolite HN 1/9 (11%) ICU 54.7 ± 10.5 Hosp
Gottschlich et al, 1990185 Critically ill burns Shriners burn formulad 2/17 (12%) ICU NR NR 9 ± 4.5
Level II (n = 31) Osmolite HN + protein 1/14 (7%) ICU 10 ± 2.5
Brown et al, 1994186 Trauma (n = 37) Experimental formulad 0/19 (0%) ICU 3/19 (16%)c NR NR
Level II Osmolite HN + protein 0/18 (0%) ICU 10/18 (56%)
Moore et al, 1994187 Trauma (n = 98) Immun-Aidb 1/51 (2%) ICU 9/51 (18%) 14.6 ± 1.3 Hospc 1.9 ± 0.9c
Level II Vivonex TEN 2/47 (4%) ICU 10/47 (21%) 17.2 ± 2.8 Hosp 5.3 ± 3.1
Immun-Aidb 5.3 ± 0.8 ICUc
Vivonex TEN 8.6 ± 3.1 ICU
Bower et al, 1995188 ICU (n = 296) Impactd 24/153 (16%) ICU 86/153 (56%) 27.6 ± 23 Hosp NR
Level I Osmolite 12/143 (8%) ICU 90/143 (63%) 30.9 ± 26 Hosp
Kudsk et al, 1996189 Trauma (n = 35) Immun-Aidb 1/17 (6%) ICU 5/16 (31%) 18.3 ± 2.8 Hospc 2.4 ± 1.3c
Level II Stand EN 1/18 (6%) ICU 11/17 (65%) 32.6 ± 7.0 Hosp 5.4 ± 2.0
Immun-Aidb 5.8 ± 1.8 ICUc
Stand EN 9.5 ± 2.3 ICU
Engel et al, 1997190 Trauma (n = 36) Impactb 7/18 (39%) ICU 6/18 (33%) 19.0 ± 7.4 ICU 14.8 ± 5.6
Level II Stand EN 5/18 (28%) ICU 5/18 (28%) 20.5 ± 5.3 ICU 16.0 ± 5.6
Mendez et al, 1997191 Trauma (n = 43) Experimental formulad 1/22 (5%) ICU 19/22 (86%)c 34.0 ± 21.2 Hospc 16.5 ± 19.4
Level II Osmolite HN + protein 1/21 (5%) ICU 12/21 (57%) 21.9 ± 11.0 Hosp 9.3 ± 6.0
Experimental formulad 18.9 ± 20.7 ICU
Osmolite HN + protein 11.1 ± 6.7 ICU
Rodrigo et al, 1997192 Mixed ICU Impactd 2/16 (13%) ICU 5/16 (31%) 8.0 ± 7.3 ICU NR
Level II (n = 30) Stand EN 1/14 (7%) ICU 3/14 (21%) 10.0 ± 2.7 ICU
Saffle et al, 1997193 Burns (n = 50) Impactd 5/25 (20%) ICU 2.36 per patient 37 ± 4 Hosp 22 ± 3
Level II Replete 3/24 (13%) ICU 1.71 per patient 38 ± 4 Hosp 21 ± 2
Weimann et al, 1998194 Trauma (n = 29) Impactd 2/16 (13%) ICU NR 70.2 ± 53 Hosp 21.4 ± 10.8
Level II Stand EN 4/13 (31%) ICU 58.1 ± 30 Hosp 27.8 ± 14.6
Impactd 31.4 ± 23.1 ICU
Stand EN 47.4 ± 32.8 ICU
Atkinson et al, 1998195 Mixed ICU Impactd 95/197 (48%) ICU 10.5 ± 13.1 ICU 8.0 ± 11.1
Level I (n = 390) Stand EN 85/193 (44%) ICU 12.2 ± 23.2 ICU 9.4 ± 17.7
Impactd 20.6 ± 26 Hosp
Stand EN 23.2 ± 32 Hosp
Galban et al, 2000196 Critically ill Impactd 17/89 (19%) ICUc 39/89 (44%) 18.2 ± 12.6 ICU 16.6 ± 12.9 12.4 ± 10.4
Level I septic (n = 176) Stand EN 28/87 (32%) ICU 44/87 (51%) ICU 12.2 ± 10.3
Caparros et al, 2001197 ICU patients Experimental formulab 27/130 (21%) ICU 64/130 (49%)c 15 (10-25) ICU 10 (5-18)
Level I (n = 235) Stand EN 30/105 (29%) ICU 37/105 (35%) 13 (9-20) ICU 9 (5-14)
Experimental formulab 29 (17-51) Hosp
Stand EN 26 (18-42) Hosp
(continued)
297
298
LOS Days, Mean ± SD Ventilator Days, Mean

Study Population Study Groups Mortality Infectionsa (or Range) ± SD (or Range)
Conejero et al, 2002198 SIRS pts (n = 84) Experimental formulab 14/47 (30%) at 28 d 11/47 (23%)c 14 (4-63) Hosp 14 (5-25)
Level II Stand EN 9/37 (24%) at 28 d 17/37 (46%) 15 (4-102) Hosp 14 (5-29)
Dent et al, 2003199 ICU (n = 170) Optimentalb 20/87 (23%) ICUc 57/87 (66%) 14.8 ± 19.6 ICU 14.3 ± 22.4
Level I Osomolite HN 8/83 (10%) ICU 52/83 (63%) 12 ± 10.9 ICU 10.8 ± 12.8
Optimentalb 25.4 ± 26 Hosp
Osomolite HN 20.9 ± 17 Hosp
Bertolini et al, 2003200 Severe sepsis Perativee 8/18 (44%) ICU NR 13.5 (9-26) Hosp NR
Level II (n = 39) Parenteral nutrition 3/21 (14%) ICU 15.0 (11-29) Hosp
Perativee 8/18 (44%) at 28 d
5/21 (24%) at 28 d
Parenteral nutrition
Chuntrasakul et al, 2003201 Trauma burns Neoimmuneg 1/18 (6%) ICU NR 3.4 ± 5.8 ICU 2.7 ± 5.2
Level II (n = 36) Traumacal (Stand EN) 1/18 (6%) ICU 7.8 ± 13.6 ICU 7.4 ± 1.3
Neoimmuneg 44.9 ± 30.2 Hosp
Traumacal (Stand EN) 28.8 ± 25.7 Hosp
Tsuei et al, 2005202 Trauma (n = 25) Stand EN + arginined 1/13 (8%) ICU 8/13 (62%) 13 ± 6 ICU 10 ± 5
Level II Stand EN + protein 0/12 (0%) ICU 6/11 (55%) 16 ± 10 ICU 14 ± 10
Stand EN + arginined 22 ± 9 Hosp
Stand EN + protein 27 ± 17 Hosp
Kieft et al, 2005203 ICU (n = 597) Stressonf 84/302 (28%) ICU 130/302 (43%) 7 (4-14) ICU 6 (3-12)
Level I 78/295 (26%) ICU
Stand EN 114/302 (38%) Hosp 123/295 (42%) 8 (5-16) ICU 6 (3-12)
Stressonf 106/295 (36%) Hosp 20 (10-35) Hosp
Stand EN 20 (10-34) Hosp

Wibbenmeyer et al, 2006204 Burn (n = 23) Cruciald 2/12 (17%) ICU 9/12 (75%) NR NR
Level II Stand EN 0/11 (0%) ICU 7/11 (64%)
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay; Hosp, hospital; SIRS, systemic inflammatory response syndrome.
a
b
Non-isonitrogenous.
c
P ≤ .05.
d
Isonitrogenous.
e
Non-isocaloric.
f
Isocaloric but non-isonitrogenous.
g
Non-isocaloric and non-isonitrogenous.
Impact, Vivonex TEN, Replete, Traumacal (Stand EN), and Crucial are all products of Nestle Nutrition U.S., Minneapolis, MN; Osmolite HN, Optimental, and
Perative are all products of Abbott Laboratories, Columbus, OH; Immun-Aid is a product of B.Braun/McGaw, Irvine, CA; and Stresson is a product of Nutricia
Clinical Care, Trowbridge, Wiltshire, Great Britain.
Table 13. Meta-Analyses Reported Comparing Immune-Modulating Enteral

Formulations to Standard Enteral Formulations
No. of
Studies General Conclusions (Effect of Immune-Modulating
Author Population Included vs Standard Enteral Formulations)
Heys et al, 1999181 Medical, surgical 11 Decreased infection (OR = 0.47, 95% CI 0.32-0.70, P < .05)
critical illness, Decreased length of stay (WMD = 2.5, 95% CI 4.0-1.0, P < .05)
cancer (n = 1009) No change in mortality (OR = 1.77, 95% CI 1.00-3.12, P = NS)
Beale et al, 1999182 Medical, surgical 12 Decreased infection (RR = 0.67, 95% CI 0.50-0.89, P = .006)
trauma, sepsis, Decreased ventilator days (WMD = 2.6, 95% CI 0.1-5.1, P = .04)
major surgery Decreased length of stay (WMD = 2.9, 95% CI 1.4-4.4, P = .0002)
(n = 1482) No change in mortality (RR = 1.05, 95% CI 0.78-1.41, P = NS)
Heyland et al, 2001210 Medical, surgical 22 Decreased infection (RR = 0.66, 95% CI 0.54-0.80, P < .05)
critical illness, major Decreased length of stay (WMD = 3.33, 95% CI 5.63-1.02, P < .05)
surgery (n = 2419) No change in mortality (RR = 1.10, 95% CI 0.93-1.31, P = NS)
Montejo et al, 2003211 Critical illness 26 Decreased abdominal abscess (OR = 0.26, 95% CI 0.12-0.55, P = .005)
(n = 1270) Decreased bacteremia (OR = 0.45, 95% CI 0.35-0.84, P = .0002)
Decreased pneumonia (OR = 0.54, 95% CI 0.35-0.84, P = .007)
Decreased ventilator days (WMD = 2.25, 95% CI 0.5-3.9, P = .009)
Decreased length of stay (WMD = 3.4, 95% CI 4.0-2.7, P < .0001)
No change in mortality (OR = 1.10, 95% CI 0.85-1.42, P = NS)
Waitzberg et al, 2006212 Elective surgery 17 Decreased infection (RR = 0.49, 95% CI 0.42-0.58, P > .0001)
(n = 2305) Decreased length of stay (WMD = 3.1, 95% CI 3.9-2.3, P < .05)
Decreased anastomotic leaks (RR = 0.56, 95% CI 0.37-0.83, P = .004)
No change in mortality (RR = 0.72, 95% CI 0.39-1.31, P = NS)
WMD, weighted mean difference; RR, relative risk; CI, confidence intervals; OR, odds ratio; NS, not significant.
septic.213,214 Based on one level I report,188 one prospec- and commercial formulations. Multiple enteral formula-
tive randomized unblinded study using a control group tions are marketed as being immune-modulating, but vary
receiving PN,200 and a third study published in abstract considerably in their makeup and dosage of individual
form only,199 use of arginine-containing formulations components. It is not clear whether the data from pub-
resulted in greater mortality than standard EN and PN lished studies and these subsequent recommendations can
formulations. Two of the 3 studies reporting a potential be extrapolated to use of formulations that have not been
adverse effect had comparatively lower levels of arginine formally evaluated. Based on the strength and uniformity
supplementation.199,200 The mechanism proposed for this of the data in surgery patients, the Guidelines Committee
adverse effect was that in severe sepsis, arginine may be felt that a grade A recommendation was warranted for use
converted to nitric oxide contributing to hemodynamic of these formulations in the surgical ICU. The reduced
instability. This concept is contradicted by 4 other reports. signal strength and heterogeneity of the data in nonop-
One of these studies showed that infusion of arginine erative critically ill patients in a medical ICU was felt to
directly into the venous circulation of septic medical and warrant a grade B recommendation.
surgical ICU patients caused no hemodynamic stability.215 For any patient who does not meet the criteria men-
Three other studies showed that clinical outcome was tioned above, there is a decreased likelihood that use of
better195,197 and mortality was reduced in moderately immune-modulating formulations will change outcome.
septic ICU patients196 with use of an arginine-containing In this situation, the added cost of these specialty formu-
formulation (compared to a standard enteral formula- lations cannot be justified and therefore standard enteral
tion). Upon review of this controversy, the Guidelines formulations should be used.180
Committee felt that immune-modulating formulations
containing arginine were safe enough to use in mild to E2. Patients with ARDS and severe acute lung injury
moderate sepsis, but that caution should be employed if (ALI) should be placed on an enteral formulation char-
utilized in patients with severe sepsis. acterized by an anti-inflammatory lipid profile (ie, ω-3
Unfortunately, few studies have addressed the indi- fish oils, borage oil) and antioxidants. (Grade: A)
vidual pharmaconutrients, their specific effects, or their
proper dosing. This body of literature has been criticized Rationale. In three level I studies involving patients with
for the heterogeneity of studies, performed in a wide range ARDS, ALI, and sepsis, use of an enteral formulation
of ICU patient populations, with a variety of experimental fortified with ω-3 fatty acids (in the form of EPA), borage
Table 14. Anti-inflammatory Immune-Modulating Enteral Nutrition (Oxepa) vs Standard Enteral Nutrition (Stand
EN) in Patients With Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury (ALI), and Sepsis
Study LOS Days, Ventilator Days, New Organ
Study Population Groups Mortality Mean ± SD Mean ± SD Dysfunction
Gadek et al, 1999207 ARDS ICU Oxepa 11/70 (16%) ICU 11.0 ± 0.9 ICUa 9.6 ± 0.9a 7/70 (10%)a
Level I (n = 146) Stand EN 19/76 (25%) ICU 14.8 ± 1.3 ICU 13.2 ± 1.4 19/76 (25%)
Oxepa 27.9 ± 2.1 Hosp
Stand EN 31.1 ± 2.4 Hosp
Singer et al, 2006208 ARDS and ALI Oxepa 14/46 (30%) at 28 da 13.5 ± 11.8 ICU 12.1 ± 11.3 NR
Level I (n = 100) Stand EN 26/49 (53%) at 28 d 15.6 ± 11.8 ICU 14.7 ± 12.0
Pontes-Arruda et al, Severe sepsis Oxepa 26/83 (31%) at 28 da 17.2 ± 4.9 ICUa 14.6 ± 4.3a 32/83 (39%)a
2006209 ICU (n = 165) Stand EN 38/82 (46%) at 28 d 23.4 ± 3.5 ICU 22.2 ± 5.1 66/82 (80%)
Level I
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay; d, day(s).
a
P ≤ .05.
Oxepa: Abbott Nutrition; Columbus, OH.
oil (γ-linolenic acid [GLA]), and antioxidants was F. Adjunctive Therapy

shown to significantly reduce length of stay in the
F1. Administration of probiotic agents has been shown
ICU, duration of mechanical ventilation, organ failure,
to improve outcome (most consistently by decreasing
and mortality compared to use of a standard enteral
infection) in specific critically ill patient populations
formulation.207-209 Controversy remains as to the optimal
involving transplantation, major abdominal surgery,
dosage, makeup of fatty acids, and ratio of individual
and severe trauma. (Grade: C) No recommendation
immune-modulating nutrients which comprise these
can currently be made for use of probiotics in the
formulations. See Table 14.207-209
general ICU population due to a lack of consistent
outcome effect. It appears that each species may have
E3. To receive optimal therapeutic benefit from the
different effects and variable impact on patient out-
immune-modulating formulations, at least 50%-65%
come, making it difficult to make broad categorical
of goal energy requirements should be delivered.
recommendations. Similarly, no recommendation can
(Grade: C)
currently be made for use of probiotics in patients
with severe acute necrotizing pancreatitis, based on
Rationale. The benefit of EN in general,5,23,136 and specifi- the disparity of evidence in the literature and the het-
cally the added value of immune-modulating agents,182,188,195 erogeneity of the bacterial strains utilized.
appears to be a dose-dependent effect. Significant differ-
ences in outcome are more likely to be seen between Rationale. Probiotics are defined as microorganisms of
groups randomized to either an immune-modulating or a human origin, which are safe, stable in the presence of
standard enteral formulation in those patients who receive gastric acid and bile salts, and when administered in ade-
a “sufficient” volume of feeding.188,195 These differences quate amounts confer a health benefit to the host. Multiple
may not be as apparent when all patients who receive any factors in the ICU induce rapid and persistent changes in
volume of feeding are included in the analysis.195 the commensal microbiota, including broad spectrum anti-
biotics, prophylaxis for stress gastropathy, vasoactive pres-
E4. If there is evidence of diarrhea, soluble fiber- sor agents, alterations in motility, and decreases in luminal
containing or small peptide formulations may be uti- nutrient delivery.217,218 These agents act by competitively
lized. (Grade: E) inhibiting pathogenic bacterial growth, blocking epithelial
attachment of invasive pathogens, eliminating pathogenic
Rationale. Those patients with persistent diarrhea (in whom toxins, enhancing mucosal barrier, and favorably modulat-
hyperosmolar agents and C. difficile have been excluded) ing the host inflammatory response.219-221 Unfortunately
may benefit from use of a soluble fiber-containing formula- for the general ICU patient population, there has not been
tion or small peptide semi-elemental formulation. The a consistent outcome benefit demonstrated. The most con-
laboratory data, theoretical concepts, and expert opinions sistent beneficial effect from use of probiotics has been a
would support the use of the small peptide enteral formu- reduction in infectious morbidity demonstrated in critically
lations but current large prospective trials are not available ill patients involving transplantation,222,223 major abdomi-
to make this a strong recommendation.216 nal surgery,224 and trauma.225,226 While some of these
Table 15. Randomized Studies Evaluating Enteral Nutrition With Glutamine (EN/GLN) vs EN Alone
Study Population Study Groups ICU Mortality Infection LOS Stay, Mean ± SD (or Range)
Houdijk et al, 1998238 Critically ill trauma EN/GLN 4/41 (10%) 20/35 (57%)a 32.7 ± 17.1 Hosp
Level II (n = 80) EN 3/39 (8%) 26/37 (70%) 33.0 ± 23.8 Hosp
Jones et al, 1999235 Mixed ICU (n = 78) EN/GLN 10/26 (38%) NR 1(4-54) ICU
Level II EN 9/24 (38%) 16.5 (5-66) ICU
Brantley et al, 2000239 Critically ill trauma EN/GLN 0/31 (0%) NR 19.5 ± 8.8 Hosp
Level II (n = 72) EN 0/41 (0%) 20.8 ± 11.5 Hosp
Hall et al, 2003236 Mixed ICU (n = 363) EN/GLN 27/179 (15%) 38/179 (21%) 25 (16-42) Hosp
Level I EN 30/184 (16%) 43/184 (23%) 30 (19-45) Hosp
Garrel et al, 2003237 Burns (n = 45) Bloodstream
Level II EN/GLN 2/21 (10%)a 7/19 (37%) 33 ± 17 Hosp
EN 12/24 (50%) 10/22 (45%) 29 ± 17 Hosp
Zhou et al, 2003240 Burns (n = 41) EN/GLN 0/20 (0%) 2/20 (10%)a 67 ± 4 Hosp
Level II EN 0/20 (0%) 6/20 (30%) 73 ± 6 Hosp
Peng et al, 2004241 Burns (n = 48) EN/GLN NR NR 46.6 ± 12.9 Hosp
Level II EN 55.7 ± 17.4 Hosp
SD, standard deviation; NR, not reported; ICU, intensive care unit; Hosp, hospital; LOS, length of stay.
a
P ≤ .05.
studies would warrant a grade B recommendation, the P = .08).232 Additional studies to delineate compatibility,
Guidelines Committee felt that the heterogeneity of the optimal dosage, route, and optimal combination of anti-
ICU populations studied, the difference in bacterial strains, oxidants are needed. Renal function should be considered
and the variability in dosing necessitated a downgrade to a when supplementing vitamins and trace elements.
grade C recommendation. As the ease and reliability of
taxonomic classification improve, stronger recommenda- F3. The addition of enteral glutamine to an EN regi-
tions for use in specific populations of critically ill patients men (not already containing supplemental glutamine)
would be expected.222,224 Probiotics in severe acute pan- should be considered in burn, trauma, and mixed ICU
creatitis are currently under scrutiny due to the results of patients. (Grade: B)
two level II single center studies showing clinical benefit
(significantly reduced infectious morbidity and hospital Rationale. See Table 15.235-241 The addition of enteral
length of stay),227,228 followed by a larger level I multicenter glutamine to an EN regimen (non-glutamine supple-
study showing increased mortality in those patients receiv- mented) has been shown to reduce hospital and ICU
ing probiotics.229 length of stay in burn and mixed ICU patients,235,237 and
mortality in burn patients alone237 compared to the same
F2. A combination of antioxidant vitamins and trace EN regimen without glutamine.
minerals (specifically including selenium) should be The glutamine powder, mixed with water to a consis-
provided to all critically ill patients receiving special- tency which allows infusion through the feeding tube,
ized nutrition therapy. (Grade: B) should be given in 2 or 3 divided doses to provide 0.3-0.5
g/kg/d. While glutamine given by the enteral route may
Rationale. Antioxidant vitamins (including vitamins E and not generate a sufficient systemic antioxidant effect, its
ascorbic acid) and trace minerals (including selenium, favorable impact on outcome may be explained by its
zinc, and copper) may improve patient outcome, espe- trophic influence on intestinal epithelium and mainte-
cially in burns, trauma, and critical illness requiring nance of gut integrity. Enteral glutamine should not be
mechanical ventilation.230,231 A meta-analysis aggregating added to an immune-modulating formulation already
data from studies evaluating various combinations of containing supplemental glutamine.237,238,240
antioxidant vitamins and trace elements showed a signifi-
cant reduction in mortality with their use (RR = 0.65; F4. Soluble fiber may be beneficial for the fully
95% CI 0.44-0.97; P =.03).232 Parenteral selenium, the resuscitated, hemodynamically stable critically ill
single antioxidant most likely to improve outcome,233,234 patient receiving EN who develops diarrhea. Insoluble
has shown a trend toward reducing mortality in patients fiber should be avoided in all critically ill patients.
with sepsis or septic shock (RR = 0.59; 95% CI 0.32-1.08; Both soluble and insoluble fiber should be avoided in
patients at high risk for bowel ischemia or severe dys- 30), the dose of PN with regard to protein and caloric
motility. (Grade: C) provision should follow the same recommendations
given for EN in guideline C5. (Grade: D)
Rationale. Three small level II studies using soluble par-
tially hydrolyzed guar gum demonstrated a significant Rationale. “Permissive underfeeding” in which the
decrease in the incidence of diarrhea in patients receiving total caloric provision is determined by 80% of energy
EN.242-244 However, no differences in days of mechanical requirements (calculated from simplistic equations such
ventilation, ICU, length of stay or multi-organ dysfunc- as 25 kcal/kg actual body weight per day, published pre-
tion syndrome (MODS) have been reported.242-244 dictive equations, or as measured by indirect calorimetry)
Insoluble fiber has not been shown to decrease the inci- will optimize efficacy of PN. This strategy avoids the
dence of diarrhea in the ICU patient. Cases of bowel potential for insulin resistance, greater infectious morbid-
obstruction in surgical and trauma patients who were ity, or prolonged duration of mechanical ventilation and
provided enteral formulations containing insoluble fiber increased hospital length of stay associated with excessive
have been reported.245,246 energy intake. In 2 studies, lower dose hypocaloric PN
was shown to reduce the incidence of hyperglycemia247
G. When Indicated, Maximize Efficacy of and infections, ICU and hospital length of stay, and dura-
tion of mechanical ventilation compared to higher euca-
Parenteral Nutrition
loric doses of PN.248 See Table 16.247-250
G1. If EN is not available or feasible, the need for
PN therapy should be evaluated (see guidelines B1, G3. In the first week of hospitalization in the ICU,
B2, B3, C3). (Grade: C) If the patient is deemed to be when PN is required and EN is not feasible, patients
a candidate for PN, steps to maximize efficacy (regard- should be given a parenteral formulation without soy-
ing dose, content, monitoring, and choice of supple- based lipids. (Grade: D)
mental additives) should be used. (Grade: C)
Rationale. This recommendation is controversial and is
Rationale. As per the discussion for guidelines B1-3 and supported by a single level II study (which was also
C3, a critically ill ICU patient may be an appropriate included in the hypocaloric vs eucaloric dosing in guide-
candidate for PN under certain circumstances: line G2 above).248 The recommendation is supported by
(1) The patient is well nourished prior to admis- animal data,251 with further support from EN studies,252
sion, but after 7 days of hospitalization, EN where long-chain fatty acids have been shown to be
has not been feasible or target goal calories immunosuppressive. Currently in North America, the
have not been met consistently by EN alone. choice of parenteral lipid emulsion is severely limited to a
(2) On admission, the patient is malnourished soy-based 18-carbon ω-6 fatty acid preparation (which
and EN is not feasible. has proinflammatory characteristics in the ICU popula-
(3) A major surgical procedure is planned, the tion). Over the first 7 days, soy-based lipid-free PN has
preoperative assessment indicates that EN is been shown to be associated with a significant reduction
not feasible through the perioperative period, in infectious morbidity (pneumonia and catheter-related
and the patient is malnourished. sepsis), decreased hospital and ICU length of stay, and
For these patients, a number of steps may be used to shorter duration of mechanical ventilation compared to
maximize the benefit or efficacy of PN while reducing its use of lipid-containing PN.248 Combining the data from
inherent risk from hyperglycemia, immune suppression, 2 studies,248,250 a meta-analysis by Heyland et al
increased oxidative stress, and potential infectious confirmed a significant reduction in infectious morbidity
morbidity.24,92 The grade of the first recommendation is (RR = 0.63; 95% CI 0.42-0.93; P = .02) in the groups
based on the strength of the literature for guidelines B1-3 receiving no soy-based lipids.21 This recommendation
and C3, while that of the second is based on the support- should be applied with caution: these 2 studies were done
ive data for guidelines G2-6. prior to the Van den Berghe studies,253,254 and full dose
PN without lipids might exacerbate stress-induced hyper-
G2. In all ICU patients receiving PN, mild permissive glycemia. While 2 favorable level II studies would gener-
underfeeding should be considered at least initially. ate a grade C recommendation, the implications from a
Once energy requirements are determined, 80% of these practical standpoint led to a downgrade of the recommen-
requirements should serve as the ultimate goal or dose dation to D. See Table 17.248,250
of parenteral feeding. (Grade: C) Eventually, as the
patient stabilizes, PN may be increased to meet energy G4. A protocol should be in place to promote moder-
requirements. (Grade: E) For obese patients (BMI ≥ ately strict control of serum glucose when providing
Table 16. Randomized Studies Evaluating Lower Hypocaloric Doses (Hypocal) of Parenteral
Nutrition (PN) vs Higher Eucaloric (Eucal) Doses of PN in Critically Ill Patients
LOS Days, Ventilator Days,
Study Mean ± SD (or Mean ± SD
Study Population Groups Mortality Infectionsa Range) (or range) Hyperglycemia
Battistella et al, 1997248 Trauma Pneumonia NR

Level II (n = 57) Hypocal 2/27 (7%) ICU 13/27 (48%)b 18 ± 12 ICUb 15 ± 12b
Eucal 0/30 (0%) ICU 22/30 (73%) 29 ± 22 ICU 27 ± 21
Bloodstream
Hypocal 5/27 (19%)b 27 ± 16 Hospb
Eucal 13/30 (43%) 39 ± 24 Hosp
Choban et al, 1997249 ICU Hypocal 0/6 (0%) Hosp NR 48 ± 30 Hosp NR NR
Level II (n = 13) Eucal 2/7 (29%) Hosp 45 ± 38 Hosp
McCowen et al, 2000250 ICU Hypocal 2/21 (10%) ICU 6/21 (29%) 19 ± 14 Hosp NR 4/21 (19%)
Level II (n = 48) Eucal 3/19 (16%) ICU 10/19 (53%) 17 ± 15 Hosp 5/19 (26%)
Ahrens et al, 2005247 SICU Hypocal 1/20 (5%) ICU 5/20 (25%) 14 (10-21) ICU 10 (4-15) 5/20 (25 %)b
Level II (n = 40) Eucal 3/20 (15%) ICU 2/20 (10%) 14 (10-37) ICU 19 (4-35) 14/20 (70%)
Hypocal 15 (11-26) Hosp
Eucal 25 (15-39) Hosp
SD, standard deviation; NR, not reported; ICU, intensive care unit; SICU, surgical ICU; Hosp, hospital; LOS, length of stay.
a
b
P ≤ .05.
Table 17. Randomized Studies Evaluating Parenteral Nutrition (PN)

With vs Without Lipids in Critically Ill Patients
Study ICU LOS Days, Ventilator Days,
Study Population Groups Mortality Infectionsa Mean ± SD Mean ± SD
Battistella et al, 1997248 Trauma (n = 57) Pneumonia

Level II Without 2/27 (7%) 13/27 (48%)b 27 ± 16 Hospb 15 ± 12b
With 0/30 (0%) 22/30 (73%) 39 ± 24 Hosp 27 ± 21
Line sepsis
5/27 (19%)b 18 ± 12 ICUb
13/30 (43%) 29 ± 22 ICU
McCowen et al, 2000250 ICU (n = 48) Without 2/21 (10%) 6/21 (29%) 19 ± 14 Hosp NR
Level II With 3/19 (16%) 10/19 (53%) 17 ± 15 Hosp
SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS, length of stay.
a
b
P ≤ .05.
nutrition support therapy. (Grade: B) A range of 110- was more pronounced in surgical ICU than medical ICU
150 mg/dL may be most appropriate. (Grade: E) patients.254 See Table 18.253-255
However, an as yet unpublished large level I multi-
Rationale. Strict glucose control, keeping serum glucose center European study suggested that moderate control
levels between 80 and 110 mg/dL, has been shown in a (keeping glucose levels between 140 and 180 mg/dL)
large single center trial to be associated with reduced might avoid problems of hypoglycemia and subsequently
sepsis, reduced ICU length of stay, and lower hospital reduce the mortality associated with hypoglycemia com-
mortality when compared to conventional insulin therapy pared to tighter control.255 With a paucity of data, the
(keeping blood glucose levels <200 mg/dL).253 The effect Guidelines Committee felt that attempting to control
Table 18. Randomized Studies Evaluating Intensive vs Moderate Control of Glucose in Critically Ill Patients
Episodes of
Study Population Study Groups Hypoglycemia Clinical Outcomes Mortality
Van den Berghe et al, 2001253 Surgical ICU Septicemia

Level I (n = 1548) Intensive controla 39/765 (51%)b 32/765 (4%) 35/765 (5%) ICUb
Conventional controlc 6/783 (1%) 61/783 (8%) 63/783 (8%) ICU
Intensive controla 55/765 (7%) Hospb
Conventional controlc 85/783 (11%) Hosp
Van den Berghe et al, 2006254 Medical ICU New kidney injury All patients at day 3
Level I (n = 1200) Intensive controla 111/595 (19%)b 35/595 (6%)b 23/595 (3.9%) ICU
c
Conventional control 19/605 (3%) 54/605 (9%) 17/605 (2.8%) ICU
Patients in ICU >3 d
Intensive controla 166/386 (43%) Hospb
Conventional controlc 200/381 (52%) Hosp
Devos et al, 2007255 Mixed ICU Intensive controla 9.8%b NR 17%
Level I (n = 1101) Moderate controld 2.7% 15%
(Mortality rate
significantly higher
in those patients
with hypoglycemia)
ICU, intensive care unit; NR, not reported; Hosp, hospital; d, day(s).
a
Intensive control: 80-110 mg/dL.
b
P < .05.
c
Conventional control: 180-200 mg/dL.
d
Moderate control: 140-180 mg/dL.
glucose in the range of 110-150 mg/dL was most appro- with stability and solubility (100 mL water per 2 g
priate at this time. glutamine).256,264-267 All 3 reports which showed a positive
clinical effect were level II studies,121,256,258 warranting a
G5. When PN is used in the critical care setting, con- grade C recommendation.
sideration should be given to supplementation with
parenteral glutamine. (Grade: C) G6. In patients stabilized on PN, periodically repeated
efforts should be made to initiate EN. As tolerance
Rationale. The addition of parenteral glutamine (at a dose improves and the volume of EN calories delivered
of 0.5 g/kg/d) to a PN regimen has been shown to reduce increases, the amount of PN calories supplied should
infectious complications,121,256 ICU length of stay,257 and be reduced. PN should not be terminated until ≥60%
mortality258 in critically ill patients, compared to the same of target energy requirements are being delivered by
PN regimen without glutamine. A meta-analysis by the enteral route. (Grade: E)
Heyland et al combining results from 9 studies confirmed
a trend toward reduced infection (RR = 0.75; 96% CI Rationale. Because of the marked benefits of EN for the
0.54-1.04; P = .08) and a significant reduction in mortal- critically ill patient, repeated efforts to initiate enteral
ity (RR = 0.67; 95% CI 0.48-0.92; P = .01) in groups therapy should be made. To avoid the complications asso-
receiving PN with parenteral glutamine versus those ciated with overfeeding, the amount of calories delivered
groups getting PN alone.21 See Table 19.121,256-264 by the parenteral route should be reduced appropriately
The proposed mechanism of this benefit relates to to compensate for the increase in the number of calories
generation of a systemic antioxidant effect, maintenance being delivered enterally. Once the provision of enteral
of gut integrity, induction of heat shock proteins, and feeding exceeds 60% of target energy requirements, PN
use as a fuel source for rapidly replicating cells. Of note, may be terminated.
the dipeptide form of parenteral glutamine upon which
most of these data are based is widely used in Europe
H. Pulmonary Failure
but not commercially available in North America (refer-
ring both to the United States and Canada). Use of H1. Specialty high-lipid low-carbohydrate formula-
L-glutamine, the only source of parenteral glutamine tions designed to manipulate the respiratory quotient
available in North America, is severely limited by problems and reduce CO2 production are not recommended for
Table 19. Randomized Studies Evaluating Parenteral Nutrition (PN) With vs Without
Supplemental Parenteral Glutamine in Critically Ill Patients
Study LOS Days, Mean ±
Study Population Groups Mortality Infectionsa SD (or Range)
Griffiths et al, 1997259 & 2002260 ICU (n = 84) With 18/42 (43%) Hosp 28/42 (67%) 10.5 (6-19) ICU
Level II Without 25/42 (60%) Hosp 26/42 (62%) 10.5 (6-24) ICU
Powell-Tuck et al, 1999261 ICU (n = 168) With 14/83 (17%) ICU NR 43.4 ± 34.1 Hosp
Level I Without 20/85 (24%) ICU 48.9 ± 38.4 Hosp
Wischmeyer et al, 2001262 Burn (n = 31) With 2/15 (13%) ICU 7/12 (58%) 40 ± 10 Hosp
Level II Without 5/16 (31%) ICU 9/14 (64%) 40 ± 9 Hosp
Goeters et al, 2002258 SICU (n = 68) With 7/33 (21%) ICU NR 21.3 ± 13.5 ICU
Level II Without 10/35 (29%) ICU 20.8 ± 9.1 ICU
With 11/33 (33%) at 6 mob 46 ± 49.1 Hosp
Without 21/35 (60%) at 6 mo 39.4 ± 31.1 Hosp
Fuentes-Orozco et al, 2004256 Peritonitis (n = 33) With 2/17 (12%) ICU 4/17 (24%)b 7.2 ± 9.2 ICU
Level II Without 3/16 (19%) ICU 12/16 (75%) 7.3 ± 4.5 ICU
With 16.5 ± 8.9 Hosp
Without 16.7 ± 7.0 Hosp
Ziegler et al, 2004257 Postop surgery (n = 63) With 1/32 (3%) Hosp 8/30 (27%) 12 ± 2 ICU Hospb
Level II Without 5/31 (16%) Hosp 13/29 (45%) 23 ± 6 ICU Hosp
Zhou et al, 2004263 Burn (n = 30) With NR 3/15 (20%) 42 ± 7.0 Hosp
Level II Without 4/15 (27%) 46 ± 6.6 Hosp
Xian-Li et al, 2004121 Acute pancreatitis With 0/20 (0%) ICU 0/20 (0%)b 25.3 ± 7.6 Hosp
Level II (n = 69) Without 3/21 (14%) ICU 5/21 (24%) 28.6 ± 6.9 Hosp
Dechelotte et al, 2006264 ICU (n = 114) With 2/58 (3%) Hosp 23/58 (40%) 12.5 (1-430) ICU
Level I Without 2/56 (4%) Hosp 32/56 (57%) 11.5 (3-121) ICU
With 16/58 (28%) at 6 mo 10/58 (17%)c 30 (1-560) Hosp
Without 9/56 (16%) at 6 mo 19/56 (34%) 26 (4-407) Hosp
SD, standard deviation; NR, not reported; ICU, intensive care unit; SICU, surgical ICU; Hosp, hospital; LOS, length of stay.
a
b
P ≤ .05.
c
Pneumonia.
routine use in ICU patients with acute respiratory caloric requirements.270 Efforts should be made to avoid
failure. (Grade: E) (This is not to be confused with total caloric provision that exceeds energy requirements,
guideline E2 for ARDS/ALI). as CO2 production increases significantly with lipogene-
sis and may be tolerated poorly in the patient prone to
Rationale. There is a lack of consensus about the opti- CO2 retention.268-270 Rapid infusion of fat emulsions
mum source and composition of lipids (medium- vs long- (especially soybean-based), regardless of the total amount,
chain triglyceride, soybean oil, olive oil, ω-3 fatty acids, should be avoided in patients suffering from severe
10% or 20% solution) in enteral and parenteral formula- pulmonary failure.
tions for the patient with respiratory failure. One small
level II study (20 patients) showed a clinical benefit H2. Fluid-restricted calorically dense formulations
(reduced duration of mechanical ventilation) from use of should be considered for patients with acute respira-
a high-fat low-carbohydrate enteral formulation com- tory failure. (Grade: E)
pared to a standard formulation.268 A second smaller level
II study (10 patients) showed no clinical benefit.269 Rationale. Fluid accumulation and pulmonary edema are
Results from uncontrolled studies suggest that increas- common in patients with acute respiratory failure and
ing the composite ratio of fat to carbohydrate becomes have been associated with poor clinical outcomes. It is
clinically significant in lowering CO2 production only in therefore suggested that a fluid-restricted calorically
the ICU patient being overfed and that composition is dense nutrient formulation (1.5-2.0 kcal/mL) be consid-
much less likely to affect CO2 production when the ered for patients with acute respiratory failure that neces-
design of the nutrition support regimen approximates sitates volume restriction.269
H3. Serum phosphate levels should be monitored as these tools are less accurate and less reliable due
closely and replaced appropriately when needed. to complications of ascites, intravascular volume
(Grade: E) depletion, edema, portal hypertension, and hypoalbu-
minemia. (Grade: E)
Rationale. Phosphate is essential for the synthesis of ade-
nosine triphosphate (ATP) and 2,3-disphosphoglycerate Rationale. While malnutrition is highly prevalent among
(2,3-DPG), both of which are critical for normal dia- patients with chronic liver disease and nearly universal
phragmatic contractility and optimal pulmonary among patients awaiting liver transplantation, the clinical
function. Length of stay and duration of mechanical consequences of liver failure render traditional nutrition
ventilation are increased in patients who become hypo- assessment tools inaccurate and unreliable. The primary
phosphatemic when compared to those who do not etiology of malnutrition is poor oral intake stemming
have this electrolyte imbalance. As suggested by several from multiple factors. Malnutrition in patients with cir-
uncontrolled studies, it therefore seems prudent to mon- rhosis leads to increased morbidity and mortality rates.
itor phosphate closely and replace appropriately when Furthermore, patients who are severely malnourished
needed.271,272 before transplant surgery have a higher rate of complica-
tions and a decreased overall survival rate after liver
transplantation. Energy needs in critically ill patients with
I. Renal Failure liver disease are highly variable, are difficult to predict by
I1. ICU patients with acute renal failure (ARF) or simple equations in liver disease, and consequently are
acute kidney injury (AKI) should be placed on stan- best determined by indirect calorimetry in ICU patients
dard enteral formulations, and standard ICU recom- with liver disease.279-287
mendations for protein and calorie provision should
be followed. If significant electrolyte abnormalities J2. EN is the preferred route of nutrition therapy in
exist or develop, a specialty formulation designed for ICU patients with acute and/or chronic liver disease.
renal failure (with appropriate electrolyte profile) may Nutrition regimens should avoid restricting protein in
be considered. (Grade: E) patients with liver failure. (Grade: E)
Rationale. ARF seldom exists as an isolated organ failure in Rationale. Nutrition therapy is essential in patients with
critically ill patients. When prescribing EN to the ICU end-stage liver disease and during all phases of liver
patient, the underlying disease process, preexisting comor- transplantation. EN has been associated with decreased
bidities, and current complications should be taken into infection rates and fewer metabolic complications in
account. Specialty formulations lower in certain electro- liver disease and after liver transplant when compared to
lytes (ie, phosphate and potassium) than standard products PN. Long-term PN can be associated with hepatic com-
may be beneficial in the ICU patient with ARF.273-275 plications, including worsening of existing cirrhosis and
liver failure with the concomitant risks of sepsis, coagul-
I2. Patients receiving hemodialysis or continuous opathy, and death. Nutrition-associated cholestasis usu-
renal replacement therapy (CRRT) should receive ally present with prolonged PN is also a significant
increased protein, up to a maximum of 2.5 g/kg/d. problem. EN improves nutrition status, reduces compli-
Protein should not be restricted in patients with renal cations, and prolongs survival in liver disease patients
insufficiency as a means to avoid or delay initiation of and is therefore recommended as the optimal route of
dialysis therapy. (Grade: C) nutrient delivery. Protein should not be restricted as a
management strategy to reduce risk of developing hepatic
Rationale. There is an approximate amino acid loss of encephalopathy.279,282 Protein requirements for the
10-15 g/d during CRRT. Providing <1 g/kg/d of protein patient with hepatic failure should be determined in the
may result in increased nitrogen deficits for patients on same manner as for the general ICU patient (in keeping
hemodialysis or CRRT. Patients undergoing CRRT should with guidelines C4 and C5).
receive formulations with 1.5-2.0 g/kg/d of protein. At
J3. Standard enteral formulations should be used in
least 1 randomized prospective trial276 has suggested an
ICU patients with acute and chronic liver disease.
intake of 2.5 g/kg/d is necessary to achieve positive nitro-
Branched chain amino acid formulations (BCAA)
gen balance in this patient population.276-278
should be reserved for the rare encephalopathic
patient who is refractory to standard treatment with
luminal acting antibiotics and lactulose. (Grade: C)
J. Hepatic Failure
J1. Traditional assessment tools should be used with Rationale. There is no evidence to suggest that a formu-
caution in patients with cirrhosis and hepatic failure, lation enriched in BCAA improves patient outcomes
compared to standard whole protein formulations in The need to initiate EN early within 24-48 hours of
critically ill patients with liver disease. Findings from admission is supported by the fact that out of six level II
level II randomized outpatient trials suggest that long- studies done only in patients with severe acute pancreati-
term (12 and 24 months) nutritional supplementation tis, 5 studies which randomized and initiated EN within
with oral BCAA granules may be useful in slowing the 48 hours of admission all showed significant outcome
progression of hepatic disease and/or failure and pro- benefits22,56,58-60 compared to PN. Only 1 study in severe
longing event-free survival. In patients with hepatic pancreatitis which randomized patients and started EN
encephalopathy refractory to usual therapy, use of BCAA after 4 days showed no significant outcome benefit.57
formulations may improve coma grade compared to stan-
dard formulations.279,288-292 K2. Patients with mild to moderate acute pancreatitis
do not require nutrition support therapy (unless an
unexpected complication develops or there is failure
K. Acute Pancreatitis
to advance to oral diet within 7 days). (Grade: C)
K1. On admission, patients with acute pancreatitis
should be evaluated for disease severity. (Grade: E) Rationale. Patients with mild to moderate acute pancrea-
Patients with severe acute pancreatitis should have a titis have a much lower rate of complications (6%) than
nasoenteric tube placed and EN initiated as soon as patients with more severe disease, have close to a 0%
fluid volume resuscitation is complete. (Grade: C) mortality rate, and have an 81% chance of advancing to
oral diet within 7 days.97,295,296 Providing nutrition support
Rationale. Based on the Atlanta Classification,293 patients therapy to these patients does not appear to change out-
with severe acute pancreatitis may be identified on admis- come. Out of three level II randomized studies which
sion by the presence of organ failure and/or the presence included patients with less disease severity (62%-81% of
of local complications within the pancreas on computer- patients had mild to moderate acute pancreatitis), none
ized tomography (CT) scan, complemented by the pres- showed significant outcome benefits with use of EN com-
ence of unfavorable prognostic signs.293,294 Organ failure pared to PN.8,46,55 Provision of nutrition support therapy
is defined by shock (systolic blood pressure <90 mm Hg), in these patients should be considered if a subsequent
pulmonary insufficiency (Pao2 <60 mm Hg), renal failure unanticipated complication develops (eg, sepsis, shock,
(serum creatinine >2 mg/dL), or GI bleeding (>500 mL organ failure) or the patient fails to advance to oral diet
blood loss within 24 hours). Local complications on CT after 7 days of hospitalization.
scan include pseudocyst, abscess, or necrosis. Unfavorable
prognostic signs are defined by an Acute Physiology and K3. Patients with severe acute pancreatitis may be fed
Chronic Health Evaluation (APACHE) II score of ≥8 or enterally by the gastric or jejunal route. (Grade: C)
by ≥3 Ranson Criteria.293,294 Patients with severe acute
pancreatitis have an increased rate of complications Rationale. Two level II prospective randomized trials com-
(38%) and a higher mortality (19%) than patients with paring gastric with jejunal feeding in patients with severe
mild to moderate disease and have close to 0% chance of acute pancreatitis showed no significant differences
advancing to oral diet within 7 days.97,295,296 Loss of gut between the 2 levels of EN infusion within the GI
integrity with increased intestinal permeability is worse tract.299,300 The success of gastric feeding in these 2 stud-
with greater disease severity.9 ies (where only 2 patients in the Eatock et al group299
Patients with severe acute pancreatitis will experi- and 1 patient in the Kumar et al group300 experienced
ence improved outcome when provided early EN. Three increased pain only without a need to reduce the infusion
meta-analyses of varying combinations of ten level II ran- rate) was attributed to early initiation of feeding within
domized trials8,22,46,54-60 showed that use of EN compared 36-48 hours of admission, thereby minimizing the degree
to PN reduces infectious morbidity (RR = 0.46; 95% CI of ileus.299
0.29-0.74; P = .001),17 hospital length of stay (WMD =
–3.94; 95% CI –5.86 to –2.02; P < .0001),17 need for K4. Tolerance to EN in patients with severe acute pan-
surgical intervention (RR = 0.48; 95% CI 0.23-0.99; P = creatitis may be enhanced by the following measures:
.05),297 multiple organ failure (OR = 0.306; 95% CI Minimizing the period of ileus after admission
0.128-0.736; P = .008),298 and mortality (OR = 0.251; by early initiation of EN. (Grade: D)
95% CI 0.095-0.666; P = .005).298 See Table 3.8,22,46,54-60 Displacing the level of infusion of EN more
In a meta-analysis of 2 studies18,19 in patients operated on distally in the GI tract. (Grade: C)
for complications of severe acute pancreatitis, there was Changing the content of the EN delivered
a trend toward reduced mortality with use of early EN from intact protein to small peptides, and
started the day after surgery (RR = 0.26; 95% CI 0.06- long-chain fatty acids to medium-chain
1.09; P =.06) compared to STD therapy where no nutri- triglycerides or a nearly fat-free elemental
tion support therapy was provided.17 formulation. (Grade: E)
Switching from bolus to continuous infusion. the choice between PN and STD therapy) becomes an
(Grade: C) important issue. In an early level II randomized trial, Sax
et al showed net harm from use of PN initiated within 24
Rationale. In a prospective level III study, Cravo et al hours of admission for patients with mild to moderate
showed that the longer the period of ileus and the greater acute pancreatitis, with significantly longer hospital
the delay in initiating EN, the worse the tolerance (and length of stay than those patients randomized to STD
the greater the need to switch to PN) in patients admitted therapy (no nutrition support therapy).97 In contrast, in a
with severe acute pancreatitis. Delays of ≥6 days resulted later level II study by Xian-Li et al in patients with severe
in 0% tolerance of EN, whereas initiating EN within 48 pancreatitis whereby PN was initiated 24-48 hours after
hours was associated with 92% tolerance.301 “full liquid resuscitation,” significant reductions in overall
Feeding higher in the GI tract is more likely to stimu- complications, hospital length of stay, and mortality were
late pancreatic exocrine secretion, which may invoke seen when compared to STD therapy.121 The design of
greater difficulties with tolerance. Conversely, feeding into this latter study may have led to a differential delay of
the jejunum 40 cm or more below the ligament of Treitz is several days in the initiation of PN, possibly after the peak
associated with little or no pancreatic exocrine stimula- of the inflammatory response.17 The grade of the first
tion.302 In a level II prospective trial, McClave et al showed recommendation (to consider use of PN) is based on the
varying degrees of tolerance with different levels of infu- results of the level II study by Xian-Li et al,121 whereas the
sion within the GI tract.46 Three patients who tolerated grade for the second recommendation (regarding the tim-
deep jejunal feeding with an EN formulation developed an ing of PN) is based on expert opinion and interpretation
uncomplicated exacerbation of symptoms with advance- of the discrepancy between these 2 reports.97,121
ment to oral clear liquids (an effect which was reversed by
return to jejunal feeding). One patient who showed toler-
L. Nutrition Therapy in End-of-Life Situations
ance to jejunal feeds had an exacerbation of the systemic
inflammatory response syndrome (SIRS) when the tube L1. Specialized nutrition therapy is not obligatory in
was displaced back into the stomach (an effect which again cases of futile care or end-of-life situations. The deci-
was reversed by return to jejunal feeding).46 sion to provide nutrition therapy should be based on
At the same level of infusion within the GI tract, effective patient/family communication, realistic
content of EN formulation may be a factor in tolerance. goals, and respect for patient autonomy. (Grade: E)
In a prospective case series, patients hospitalized for
acute pancreatitis who could not tolerate a regular diet Rationale. Healthcare providers are not obligated to initi-
showed resolution of symptoms and normalization of ate nutrition support therapy in end-of-life situations.
amylase levels after switching to an oral, nearly fat-free Dehydration and starvation are well tolerated and gener-
elemental EN formulation.303 In a patient operated on for ate little symptomatology in the vast majority of patients.
complications of severe acute pancreatitis, feeding a In this unfortunate setting, provision of EN or PN ther-
nearly fat-free elemental EN formulation had signifi- apy has not been shown to improve outcome. Nonetheless,
cantly less pancreatic exocrine stimulation (measured by cultural, ethnic, religious, or individual patient issues
lipase output from the ampulla) than a standard EN for- may in some circumstances necessitate delivery of nutri-
mulation with intact long-chain fatty acids infused at the tion support therapy.306,307
same level of the jejunum.304
The manner of infusion of EN also affects tolerance.
A small level II randomized trial showed that continuous Acknowledgments
infusion of EN into the jejunum (100 mL over 60 min-
utes) was associated with significantly less volume, bicar- The Canadian Clinical Practice Guidelines (CPGs)21 served
bonate, and enzyme output from the pancreas than the as an indispensable reference source and a valuable model
same volume given as an immediate bolus.305 It is not for the organization of the topics included in this docu-
clear whether the data from this study can be extrapo- ment. Many of the tables were adapted from the CPGs.
lated to gastric feeding. (Note: The Guidelines Committee
does not recommend bolus feeding into the jejunum.) Authors’ Disclosures—Potential
K5. For the patient with severe acute pancreatitis,
Conflicts of Interest
when EN is not feasible, use of PN should be consid- Speaker’s bureaus, consultant fees, or research
ered. (Grade: C) PN should not be initiated until after grants: Stephen A. McClave, MD (Nestle, Abbott, ACM
the first 5 days of hospitalization. (Grade: E) Technologies, Kimberly-Clark, Microvasive Boston Scientific);
Robert G. Martindale, MD (Nestle, Abbott, Merck); Beth
Rationale. For patients with severe acute pancreatitis, Taylor, RD (Nestle); Pamela Roberts, MD (Nestle and
when EN is not feasible, timing of initiation of PN (and Abbott); and Juan Ochoa, MD (Nestle and Abbott).
Direct financial interest—stock ($10,000 or immunity by reducing lymphotoxin beta receptor expression. Ann
more): none. Surg. 2006;244:392-399.
8. Windsor AC, Kanwar S, Li AG, et al. Compared with parenteral
Authors with no relationship to disclose: Vincent W. nutrition, enteral feeding attenuates the acute phase response
Vanek, MD; Gail Cresci, RD; Mary McCarthy, RN, PhD; and improves disease severity in acute pancreatitis. Gut. 1998;42:
and Lena M. Napolitano, MD. 431-435.
9. Ammori BJ, Leeder PC, King RF, et al. Early increase in intestinal
permeability in patients with severe acute pancreatitis: correlation
A.S.P.E.N. Board of Directors with endotoxemia, organ failure, and mortality. J Gastrointest Surg.
1999;3:252-262.
Providing Final Approval
10. Lewis SJ, Egger M, Sylvester PA, et al. Early enteral feeding
Kelly A. Tappenden, RD, PhD; Vincent W. Vanek, MD; versus “nil by mouth” after gastrointestinal surgery: systematic review
and meta-analysis of controlled studies. Br Med J. 2001;323:1-5.
Stephen A. McClave, MD; Jay M. Mirtallo, RPh, BSNSP;
11. Schroeder D, Gillanders L, Mahr K, Hill GL. Effects of immediate
Ainsley M. Malone, RD, MS; Lawrence A. Robinson, postoperative enteral nutrition on body composition, muscle func-
PharmD; Charles Van Way III, MD; Elizabeth M. Lyman, tion, and wound healing. JPEN J Parenter Enteral Nutr. 1991;15:
RN, MSN; John R. Wesley, MD; Mark R. Corkins, MD; 376-383.
and Tom Jaksic, MD, PhD. 12. Sagar S, Harland P, Shields R. Early postoperative feeding with
elemental diet. Br Med J. 1979;1:293-295.
13. Carr CS, Ling KD, Boulos P, Singer M. Randomised trial of safety
SCCM Council Providing Final Approval and efficacy of immediate postoperative enteral feeding in patients
undergoing gastrointestinal resection. BMJ. 1996;12:869-871.
Philip S. Barie, MD, MBA; Mitchell M. Levy, MD; Judith 14. Beier-Holgersen R, Boesby S. Influence of postoperative enteral
Jacobi, PharmD; Pamela A. Lipsett, MD; Frederick P. nutrition on postsurgical infections. Gut. 1996;39:833-835.
15. Heslin MJ, Latkany L, Leung D, et al. A prospective, randomized
Ognibene, MD; Alice D. Ackerman, MD; Thomas P.
trial of early enteral feeding after resection of upper gastrointesti-
Bleck, MD; Richard J. Brilli, MD; Craig M. Coopersmith, nal malignancy. Ann Surg. 1997;226:567-577.
MD; Joseph F. Dasta, MSc; Clifford S. Deutschman, 16. Watters JM, Kirkpatrick SM, Norris SB, Shamji FM, Wells GA.
MD; Todd Dorman, MD; J. Christopher Farmer, MD; Immediate postoperative enteral feeding results in impaired
Heidi L. Frankel, MD; Steven J. Martin, PharmD; Barbara respiratory mechanics and decreased mobility. Ann Surg. 1997;226:
369-377.
McLean, MN, CCRN, CCNS-NP; Carol Thompson,
17. McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition sup-
PhD, CCRN; and Janice L. Zimmerman, MD. port in acute pancreatitis: a systematic review of the literature.
JPEN J Parenter Enteral Nutr. 2006;30:143-156.
18. Pupelis G, Austrums E, Jansone A, Sprucs R, Wehbi H. Randomised
American College of Critical Care Medicine trial of safety and efficacy of postoperative enteral feeding in
Board of Regents Providing Final Approval patients with severe pancreatitis: preliminary report. Eur J Surg.
2000;166:383-387.
Antoinette Spevetz, MD; Timothy S. Yeh, MD; M. Michele 19. Pupelis G, Selga G, Austrums E, Kaminski A. Jejunal feeding, even
Moss, MD; Lena M. Napolitano, MD; E. Daleen Aragon, when instituted late, improves outcomes in patients with severe
RN, PhD, CCRN; Sandralee A. Blosser, MD; Richard D. pancreatitis and peritonitis. Nutrition. 2001;17:91-94.
20. Kudsk KA, Croce MA, Fabian TC, et al. Enteral versus parenteral
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Canadian Critical Care Clinical Practice Guidelines Committee.
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Journal of Parenteral and

Guidelines for the Provision and

Assessment of Nutrition Support Therapy Society of Critical Care Medicine

in the Adult Critically Ill Patient:

Society of Critical Care Medicine (SCCM) and American

Preliminary Remarks Periodic Guideline Review and Update

Table 1. Grading System Used for These Guidelines

grade for the recommendation was based on the number Introduction

LOS Days, Mean ± SD Other Clinical

Braga et al, 200151 Surgery GI Complications

Montecalvo et al, MICU/SICU (n = 38) Duration MV, % Goal feeds

Kortbeek et al, Trauma (n = 80) Duration MV, Time to goal feeds

Day et al, 200186 ICU (n = 25) NR NR NR # tubes replaced

Montejo et al, ICU (n = 101) NR % Goal feeds by

Table 7. Randomized Studies Evaluating Enteral Nutrition (EN) vs EN Supplemented

Herndon et al, Burn EN+PN 8/13 (62%) ICU NR NR NR NR

Table 9. Randomized Studies Evaluating Body Position During Tube Feeding

Hiebert et al, NR Time to goal calories Diarrhea (stool frequency)

LOS Days, Mean ± SD Ventilator Days, Mean

Stand EN 20 (10-34) Hosp

Table 13. Meta-Analyses Reported Comparing Immune-Modulating Enteral

oil (γ-linolenic acid [GLA]), and antioxidants was F. Adjunctive Therapy

Battistella et al, 1997248 Trauma Pneumonia NR

Table 17. Randomized Studies Evaluating Parenteral Nutrition (PN)

Battistella et al, 1997248 Trauma (n = 57) Pneumonia

Van den Berghe et al, 2001253 Surgical ICU Septicemia

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