Volume 33, Issue 3 p. 277-316
Clinical Guideline
Free Access

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient:

Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)

Stephen A. McClave MD

Corresponding Author

Stephen A. McClave MD

Address correspondence to: Steven A. McClave, MD, Division of Gastroenterology/Hepatology, University of Louisville, 550 South Jackson Street, Louisville, KY 40292; email: [email protected].Search for more papers by this author
Robert G. Martindale MD, PhD

Robert G. Martindale MD, PhD

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Vincent W. Vanek MDMary McCarthy RN, PhDPamela Roberts MDBeth Taylor RDJuan B. Ochoa MDLena Napolitano MDGail Cresci RDthe A.S.P.E.N. Board of Directors

the A.S.P.E.N. Board of Directors

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the American College of Critical Care Medicine

the American College of Critical Care Medicine

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First published: 27 April 2009
Citations: 1,287

Preliminary Remarks

Guideline Limitation

Practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival.

The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines.

The guidelines offer basic recommendations that are supported by review and analysis of the pertinent available current literature, by other national and international guidelines, and by the blend of expert opinion and clinical practicality. The “intensive care unit” (ICU) or “critically ill” patient is not a homogeneous population. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in definition of disease state and severity of illness, lack of baseline nutrition status, and lack of statistical power for analysis. Whenever possible, these factors are taken into account and the grade of statement will reflect the power of the data. One of the major methodological problems with any guideline is defining the exact population to be included.

Periodic Guideline Review and Update

These guidelines may be subject to periodic review and revision based on new peer-reviewed critical care nutrition literature and practice.

Target Patient Population for Guideline

These guidelines are intended for the adult medical and surgical critically ill patient populations expected to require an ICU stay of > 2 or 3 days and are not intended for those patients in the ICU for temporary monitoring or those who have minimal metabolic or traumatic stress. These guidelines are based on populations, but like any other therapeutic treatment in an ICU patient, nutrition requirements and techniques of access should be tailored to the individual patient.

Target Audience

The intended use of these guidelines is for all individuals involved in the nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, pharmacists, and respiratory and physical therapists where indicated.

Methodology

A list of guideline recommendations was compiled by the experts on the Guidelines Committee for the 2 societies, each of which represented clinically applicable definitive statements of care or specific action statements. Prospective randomized controlled trials were used as the primary source to support guideline statements, with each study being evaluated and given a level of evidence. The overall grade for the recommendation was based on the number and level of investigative studies referable to that guideline. Large studies warranting level I evidence were defined as those with ≥100 patients or those which fulfilled endpoint criteria predetermined by power analysis. The level of evidence for uncontrolled studies was determined by whether they included contemporaneous controls (level III), historical controls (level IV), or no controls (level V, equal to expert opinion). See Table 1 . 1

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 offalse-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 bypower analysis. Meta-analyses were used to organize information and to drawconclusions about overall treatment effect from multiple studies on aparticular subject. The grade of recommendation, however, was based on thelevel of evidence of the individual studies. Reproduced from Dellinger RP, Carlet JM, Masur H. Introduction. CritCare Med. 2004;32(11)(suppl):S446 with permission of the publisher.Copyright 2004 Society of Critical Care Medicine.

Review papers and consensus statements were considered expert opinion and were designated the appropriate level of evidence. Meta-analyses were used to organize the information and to draw conclusions about an 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. An A or B grade recommendation required at least 1 or 2 large positive randomized trials supporting the claim, while a C grade recommendation required only 1 small supportive randomized investigation. The rationale for each guideline statement was used to clarify certain points from the studies, to identify controversies, and to provide clarity in the derivation of the final recommendation. Significant controversies in interpretation of the literature were resolved by consensus of opinion of the committee members, which in some cases led to a downgrade of the recommendation. Following an extensive review process by external reviewers, the final guideline manuscript was reviewed and approved by A.S.P.E.N. Board of Directors and SCCM's Board of Regents and Council.

Introduction

The significance of nutrition in the hospital setting cannot be overstated. This significance is particularly noted in the ICU. Critical illness is typically associated with a catabolic stress state in which patients commonly demonstrate a systemic inflammatory response. This response is coupled with complications of increased infectious morbidity, multi-organ dysfunction, prolonged hospitalization, and disproportionate mortality. Over the past 3 decades, the understanding of the molecular and biological effects of nutrients in maintaining homeostasis in the critically ill population has made exponential advances. Traditionally, nutrition support in the critically ill population was regarded as adjunctive care designed to provide exogenous fuels to support the patient during the stress response. This support had 3 main objectives: to preserve lean body mass, to maintain immune function, and to avert metabolic complications. Recently these goals have become more focused on nutrition therapy, specifically attempting to attenuate the metabolic response to stress, to prevent oxidative cellular injury, and to favorably modulate the immune response. Nutritional modulation of the stress response to critical illness includes early enteral nutrition, appropriate macro- and micronutrient delivery, and meticulous glycemic control. Delivering early nutrition support therapy, primarily using the enteral route, is seen as a proactive therapeutic strategy that may reduce disease severity, diminish complications, decrease length of stay in the ICU, and favorably impact patient outcome.

A. Initiate Enteral Feeding

A1. Traditional nutrition assessment tools (albumin, prealbumin, and anthropometry) are not validated in critical care. Before initiation of feedings, assessment should include evaluation of weight loss and previous nutrient intake prior to admission, level of disease severity, comorbid conditions, and function of the gastrointestinal (GI) tract. (Grade: E)

Rationale. In the critical care setting, the traditional protein markers (albumin, prealbumin, transferrin, retinol binding protein) are a reflection of the acute phase response (increases in vascular permeability and reprioritization of hepatic protein synthesis) and do not accurately represent nutrition status in the ICU setting. Anthropometrics are not reliable in assessment of nutrition status or adequacy of nutrition therapy.2,3

A2. Nutrition support therapy in the form of enteral nutrition (EN) should be initiated in the critically ill patient who is unable to maintain volitional intake. (Grade: C)

Rationale. EN supports the functional integrity of the gut by maintaining tight junctions between the intraepithelial cells, stimulating blood flow, and inducing the release of trophic endogenous agents (such as cholecystokinin, gastrin, bombesin, and bile salts). EN maintains structural integrity by maintaining villous height and supporting the mass of secretory IgA-producing immunocytes which comprise the gut-associated lymphoid tissue (GALT) and in turn contribute to mucosal-associated lymphoid tissue (MALT) at distant sites such as the lungs, liver, and kidneys.4-7

Adverse change in gut permeability from loss of functional integrity is a dynamic phenomenon which is time-dependent (channels opening within hours of the major insult or injury). The consequences of the permeability changes include increased bacterial challenge (engagement of GALT with enteric organisms), risk for systemic infection, and greater likelihood of multi-organ dysfunction syndrome (MODS).4,5 As disease severity worsens, increases in gut permeability are amplified and the enteral route of feeding is more likely to favorably impact outcome parameters of infection, organ failure, and hospital length of stay (compared to the parenteral route).8

The specific reasons for providing early EN are to maintain gut integrity, modulate stress and the systemic immune response, and attenuate disease severity.6,8,9 Additional endpoints of EN therapy include use of the gut as a conduit for the delivery of immune-modulating agents and use of enteral formulations as an effective means for stress ulcer prophylaxis.

Nutrition support therapy (also called “specialized” or“ artificial” nutrition therapy) refers to the provision of enteral tube feeding or parenteral nutrition. “Standard therapy” refers to a patient's own volitional intake without provision of specialized nutrition support therapy. The importance of promoting gut integrity with regard to patient outcome is being strengthened by clinical trials comparing critically ill patients fed by EN to those receiving standard (STD) therapy. In a recent meta-analysis10 in elective gastrointestinal surgery and surgical critical care, patients undergoing a major operation who were given early postoperative EN experienced significant reductions in infection (relative risk [RR] = 0.72; 95% confidence interval [CI] 0.54-0.98; P = .03), hospital length of stay (mean 0.84 days; range 0.36-1.33 days; P = .001), and a trend toward reduced anastomotic dehiscence (RR = 0.53; 95% CI 0.26-1.08; P = .08), when compared to similar patients receiving no nutrition support therapy.10-16 In a meta-analysis17 of patients undergoing surgery for complications of severe acute pancreatitis, those placed on EN 1 day postop showed a trend toward reduced mortality compared to controls randomized to STD therapy (RR = 0.26; 95% CI 0.06-1.09; P = .06).17-19 See Table 2 . 11-16,18,19

Table 2. Randomized Studies Evaluating Enteral Nutrition (EN) vs No NutritionSupport Therapy (Standard [STD] Therapy) in Elective Surgery, Surgery CriticalCare, and Acute Pancreatitis Patients
Study Population Study Groups Infectiona Hospital LOS Days, Mean ± SD (or Range) Hospital Mortality Other Outcomes
Sagar et al, 197912Level II GI surgery (n = 30) EN 3/15 (20%) 14 (10-26) 0/15 (0%)
STD 5/15 (33%) 19 (10-46) 0/15 (0%)
Schroeder et al,199111 Level II GI surgery (n = 32) Anastomotic dehiscence
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, 199613Level II GI surgery (n = 28) Lactulose:mannitol ratio
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,199614 Level II GI surgery (n = 60) Anastomotic leak
EN 2/30b (7%) 8.0c 2/30 (7%) 2/30 (7%)
STD 14/30 (47%) 11.5 4/30 (13%) 4/30 (13%)
Heslin et al,199715 Level I GI surgery (n = 195) Major complication
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 Level II GI surgery (n = 28) Anastomotic leak
EN NR 17 ± 9 0 (0%) 1/13 (8%)
STD 16 ± 7 0 (0%) 3/15 (20%)
Pupelis et al,200018 Level II Acute pancreatitis (n = 29) EN 3/11 (27%) 45 ± 96 1/11 (9%)
STD 1/18 (6%) 29 ± 103 5/18 (28%)
Pupelis et al,200119 Level II Acute pancreatitis, peritonitis (n = 60) MOF
EN 10/30 (33%)d 35.3 ± 22.9 1/30 (3%) 18/30 (60%)
STD 8/30 (27%) 35.8 ± 32.5 7/30 (23%) 20/30 (67%)
  • 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 unlessotherwise stated.
  • b P ≤ .05.
  • c P = .08.
  • d Wound sepsis.

A3. EN is the preferred route of feeding over parenteral nutrition (PN) for the critically ill patient who requires nutrition support therapy. (Grade: B)

Rationale. In the majority of critically ill patients, it is practical and safe to utilize EN instead of PN. The beneficial effects of EN when compared to PN are well documented in numerous prospective randomized controlled trials involving a variety of patient populations in critical illness, including trauma, burns, head injury, major surgery, and acute pancreatitis.8,20-22 While few studies have shown a differential effect on mortality, the most consistent outcome effect from EN is a reduction in infectious morbidity (generally pneumonia and central line infections in most patient populations, and specifically abdominal abscess in trauma patients).20 In many studies, further benefits are seen from significant reductions in hospital length of stay,21 cost of nutrition therapy,21 and even return of cognitive function (in head injury patients).23 All 6 meta-analyses that compared EN to PN showed significant reductions in infectious morbidity with use of EN.21,24-28 Noninfective complications (risk difference = 4.9; 95% CI 0.3-9.5; P =.04) and reduced hospital length of stay (weighted mean difference [WMD] = 1.20 days; 95% CI 0.38-2.03; P = .004) were seen with use of EN compared to PN in 1 metaanalysis by Peter et al.28 Five of the meta-analyses showed no difference in mortality between the 2 routes of nutrition support therapy.21,24,26-28 One meta-analysis by Simpson and Doig25 showed a significantly lower mortality (RR = 0.51; 95% CI 0.27-0.97; P =.04) despite a significantly higher incidence of infectious complications (RR = 1.66; 95% CI 1.09-2.51; P =.02) with use of PN compared to EN.25 See Table 3 . 8,20,22,29-61

Table 3. Randomized Studies Evaluating Enteral Nutrition (EN) vs ParenteralNutrition (PN) in Surgery, Trauma, Pancreatitis, and Critically IllPatients
Study Population Study Groups ICU Mortality Infectionsa LOS Days, Mean ± SD (or Range) Other Clinical Outcomes Cost
Rapp et al, 198329Level II ICU head injury (n = 38) Duration MV NR
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, 198630Level II Trauma (n = 46) Duration MV
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, 198631Level II GI surgery (n = 20) Complications
EN 0/10 (0%) 0/10 (0%) 0/10 (0%)
PN 0/10 (0%) 0/10 (0%) 0/10 (0%)
Szeluga et al,198732 Level II Bone marrow transplant (n = 61) No difference at 100 days and long-term Complications
EN 5/30 (17%) 33 ± 15 Hosp 11/30 (37%) $1139/patient
PN 8/31 (26%) 36 ± 18 Hosp 14/31 (45%) $2575/patient
Young et al, 198733Level II ICU head injury (n = 58) EN 10/28 (36%) 5/28 (18%) NR NR NR
PN 10/23 (43%) 4/23 (17%)
Peterson et al,198834 Level II Trauma (n = 59) EN NR 2/21 (10%) 13.2 ± 1.6 Hosp NR NR
PN 8/25 (32%) 14.6 ± 1.9 Hosp
EN 3.7 ± 0.8 ICU
PN 4.6 ± 1.0 ICU
Cerra et al, 198835Level II ICU (n = 70) Complications
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 Level II Inflammatory bowel (n = 51) Complications
EN 0/19 (0%) 0/19 (0%) 0/19 (0%)
PN 0/32 (0%) 0/32 (0%) 0/32 (0%)
Moore et al, 198937Level II Trauma (n = 75) EN 0/29 (0%) 5/29 (17%) NR NR
PN 0/30 (0%) 11/30 (37%)
Hamaoui et al,199038 Level II GI surgery (n = 19) EN 1/11 (9%) 1/11 (9%) 0/11 (0%) $44.36/db
PN 0/8 (0%) 0/8 (0%) 0/8 (0%) $102.10/d
Kudsk et al, 199220Level II Trauma (n = 98) Duration MV NR
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,199339 Level II Inflammatory bowel (n = 44) Complications
EN 0/23 (0%) 1/23 (4%) 11/23 (48%)
PN 0/21 (0%) 8/21 (38%) 11/21 (52%)
Iovinelli et al,199340 Level II Head—neck cancer (n = 48) Complications
EN 0/24 (0%) 5/24 (21%) 26 ± 11bHosp 1/24 (4%)
PN 0/24 (0%) 4/24 (17%) 34 ± 11 Hosp 2/24 (8%)
Kudsk et al, 199441Level II Trauma (n = 68) Complications
EN 1/34 (3%) 5/34 (15%) 0/34 (0%)
PN 0/34 (0%) 14/34 (41%) 0/34 (0%)
Dunham et al,199442 Level II Trauma (n = 37) NR Complications NR
EN 1/12 (8%) 0/12 (0%) 0/12 (0%)
PN 1/15 (7%) 0/15 (0%) 0/15 (0%)
Borzotta et al,199443 Level II Neurotrauma (n = 59) EN 5/28 (18%) 51 per group 39 ± 23.1 Hosp NR $121,941b
PN 1/21 (5%) 39 per group 36.9 ± 14 Hosp $112,450
Hadfield et al,199544 Level II ICU (n = 24) EN 2/13 (15%) NR NR NR NR
PN 6/11 (55%)
Baigrie et al,199645 Level II GI surgery (n = 97) Complications
EN 4/50 (8%) 2/50 (4%) 15/50 (30%)
PN 6/47 (13%) 10/47 (21%) 23/47 (49%)
McClave et al,199746 Level II Acute pancreatitis (n = 32) EN 0/16 (0%) 2/16 (13%) 9.7 ± 1.3 Hosp NR $761 ±50.3b
PN 0/16 (0%) 2/16 (13%) 11.9 ± 2.6 Hosp $3294 ± 551.9
Reynolds et al,199747 Level II Trauma (n = 67) Complications
EN 2/33 (6%) 10/33 (30%) 11/33 (33%)
PN 1/34 (3%) 19/34 (56%) 6/34 (18%)
Sand et al, 199748Level II GI surgery (n = 29) Complications
EN 0/13 (0%) 3/13 (23%) 3/13 (23%) Cost of PN was 4 × cost of EN
PN 1/16 (6%) 5/16 (31%) 3/16 (19%)
Kalfarentzos et al,199722 Level II Acute pancreatitis (n = 38) EN 1/18 (6%) 5/18 (28%)b 40 (25-83) Hosp Savings of 70 GBP/d withENb
PN 2/20 (10%) 10/20 (50%) 39 (22-73) Hosp
Duration MV
EN 11 (5-21) ICU 15 (6-16) d
PN 12 (5-24) ICU 11 (7-31) d
Gianotti et al,199749 Level I Surgery GI cancer (n = 176) EN 0/87 (0%) 20/87 (23%)c 19.2 ± 7.9 Hosp NR
PN 0/86 (0%) 24/86 (28%) 21.6 ± 8.9 Hosp
Windsor et al, 19988Level II Acute pancreatitis (n = 34) MOF NR
EN 0/16 (0%) 0/16 (0%) 12.5 (9.5-14) Hosp 0/16 (0%)
PN 2/18 (11%) 3/18 (17%) 15.0 (11-28) Hosp 5/18 (28%)
Woodcock et al,200150 Level II ICU patients (n = 38) EN 9/17 (53%) 6/16 (38%) 33.2 ± 43 Hosp NR NR
PN 5/21 (24%) 11/21 (52%) 27.3 ± 18.7 Hosp
Braga et al, 200151Level I Surgery GI cancer (n = 257) Complications
EN 3/126 (2%) 25/126 (20%) 19.9 ± 8.2 Hosp 45/126 (36%) $25/d
PN 4/131 (3%) 30/131 (23%) 20.7 ± 8.8 Hosp 53/131 (40%) $90/d
Pacelli et al,200152 Level I Major surgery (n = 241) Postop complications NR
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%)
Bozzetti et al,200153 Level I Surgery GI cancer (n = 317) Postop complications NR
EN 2/159 (1.3%) 25/159 (16%)b 13.4 ± 4.1Hospb 54/159 (34%)b
PN 5/158 (3.2%) 42/158 (27%) 15.0 ± 5.6 Hosp 78/158 (49%)
Oláh et al,200254 Level II Acute pancreatitis (n = 89) MOF NR
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 Level II Acute pancreatitis (n = 53) MOF
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, 200356Level II Acute pancreatitis (n = 17) MOF
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, 200557Level II Acute pancreatitis (n = 28) MOF
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
Petrov et al,200658 Level II Acute pancreatitis (n = 70) Pancreas MOF NR
EN 2/35 (6%) 7/35 (20%)b NR 7/35 (20%)b
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 Level II Acute pancreatitis (n = 48) MOF NR
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%)
Casas et al, 200760 Level II Acute pancreatitis (n = 22) MOF NR
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, mechanicalventilation; neuro, neurologic; MOF, multiple organ failure; GI,gastrointestinal; Postop, postoperative; d, days. Adapted from the Canadian Clinical PracticeGuidelines,21McClave et al,17and adapted with permission from Braunschweig et al, Am J Clin Nutr.2001;74:534-542, American Society for Nutrition.
  • a All infections represent number of patients per group with infection unlessotherwise stated.
  • b P ≤ .05.
  • c P = .08.

A4. Enteral feeding should be started early within the first 24-48 hours following admission. (Grade: C) The feedings should be advanced toward goal over the next 48-72 hours. (Grade: E)

Rationale. Attaining access and initiating EN should be considered as soon as fluid resuscitation is completed and the patient is hemodynamically stable. A “window of opportunity” exists in the first 24-72 hours following admission or the onset of a hypermetabolic insult. Feedings started within this time frame (compared to feedings started after 72 hours) are associated with less gut permeability, diminished activation, and release of inflammatory cytokines (ie, tumor necrosis factor [TNF] and reduced systemic endotoxemia).21 One meta-analysis by Heyland et al showed a trend toward reduced infectious morbidity (RR = 0.66; 95% CI 0.36-1.22; P =.08) and mortality (RR = 0.52; 95% CI 0.25-1.08; P = .08),21 while a second by Marik and Zaloga showed significant reductions in infectious morbidity (RR = 0.45; 95% CI 0.30-0.66; P = .00006) and hospital length of stay (mean 2.2 days, 95% CI 0.81-3.63 days; P = .001) with early EN compared to delayed feedings.62 See Table 4 . 63-72

Table 4. Randomized Studies Evaluating Early Enteral Nutrition (EN) vs DelayedEN in Critically Ill Patients
Study Population Study Groups ICU Mortality Infectionsa LOS Days, Mean ± SD Ventilator Days, Mean ± SD Cost
Moore et al, 198663Level II Trauma (n = 43) Early 1/32 (3%) 3/32 (9%) NR NR $16,280 ± 2146
Delayed 2/31 (6%) 9/31 (29%) $19,636 ± 3396
Chiarelli et al,199064 Level II Burn (n = 20) Early 0/10 (0%) 3/10 (30%)b 69.2 ±10.4c Hosp NR NR
Delayed 0/10 (0%) 7/10 (70%) 89.0 ± 18.9 Hosp
Eyer et al, 199365Level II SICU trauma (n = 52) Early 2/19 (11%) 29 per group 11.8 ± 7.9 ICU 10.2 ± 8.1 NR
Delayed 2/19 (11%) 14 per group 9.9 ± 6.7 ICU 8.1 ± 6.8
Chuntrasakul et al,199666 Level II SICU trauma (n = 38) Early 1/21 (5%) NR 8.1 ± 6.3 ICU 5.29 ± 6.3 NR
Delayed 3/17 (18%) 8.4 ± 4.8 ICU 6.12 ± 5.3
Singh et al, 199867Level II Peritonitis (n = 43) Early 4/21 (19%) 7/21 (33%) 14 ± 6.9 Hosp NR NR
Delayed 4/22 (18%) 12/22 (55%) 13 ± 7.0 Hosp
Minard et al,200068 Level II Closed head injury (n = 27) Early 1/12 (8%) 6/12 (50%) 30 ± 14.7 Hosp 15.1 ± 7.5 NR
Delayed 4/15(27%) 7/15 (47%) 21.3 ± 13.7 Hosp 10.4 ± 6.1
Early 18.5 ± 8.8ICUc
Delayed 11.3 ± 6.1 ICU
Kompan et al,200469 Level II SICU trauma (n = 52) Early 0/27 (0%) 9/27 (33%) 15.9 ± 9.7 ICU 12.9 ± 8.1 NR
Delayed 1/25 (4%) 16/25 (64%) 20.6 ± 18.5 ICU 15.6 ± 16.1
Malhotra et al,200470 Level I Postop peritonitis (n = 200) Early 12/100 (12%) 54/100 (54%) 10.6 Hosp NR NR
Delayed 16/100 (16%) 67/100 (67%) 10.7 Hosp
Early 1.6 ICU
Delayed 2.1 ICU
Peck et al, 200471Level II Burn (n = 27) Early 4/14 (29%) 12/14 (86%) 60 ± 44 Hosp 32 ± 27 NR
Delayed 5/13 (38%) 11/13 (85%) 60 ± 38 Hosp 23 ± 26
Early 40 ±32 ICU
Delayed 37 ± 33 ICU
Dvorak et al,200472 Level II Spinal cord injury (n = 17) Early 0/7 (0%) 2.4 ± 1.5 per pt 53 ± 34.4 Hosp 31.8 ± 35.0 NR
Delayed 0/10 (0%) 1.7 ±1.1 per pt 37.9 ± 14.6 Hosp 20.9 ± 14.4
  • SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS,length of stay; Hosp, hospital; SICU, surgical ICU; pt, patient. Adapted from the Canadian Clinical PracticeGuidelines.21
  • a All infections represent number of patients per group with infection unlessotherwise stated.
  • b Bacteremia.
  • c P ≤ .05.

A5. In the setting of hemodynamic compromise (patients requiring significant hemodynamic support including high dose catecholamine agents, alone or in combination with large volume fluid or blood product resuscitation to maintain cellular perfusion), EN should be withheld until the patient is fully resuscitated and/or stable. (Grade: E)

Rationale. At the height of critical illness, EN is being provided to patients who are prone to GI dysmotility, sepsis, and hypotension and thus are at increased risk for subclinical ischemia/reperfusion injury involving the intestinal microcirculation. Ischemic bowel is a rare complication of EN, occurring in <1% of cases.73,74 EN-related ischemic bowel has been reported most often in the past with use of surgical jejunostomy tubes. However, more recently, this complication has been described with use of nasojejunal tubes.75 EN intended to be infused into the small bowel should be withheld in patients who are hypotensive (mean arterial blood pressure <60 mm Hg), particularly if clinicians are initiating use of catecholamine agents (eg, norepinephrine, phenylephrine, epinephrine, dopamine) or escalating the dose of such agents to maintain hemodynamic stability. EN may be provided with caution to patients into either the stomach or small bowel on stable low doses of pressor agents,76 but any signs of intolerance (abdominal distention, increasing nasogastric tube output or gastric residual volumes, decreased passage of stool and flatus, hypoactive bowel sounds, increasing metabolic acidosis and/or base deficit) should be closely scrutinized as possible early signs of gut ischemia.

A6. In the ICU patient population, neither the presence nor absence of bowel sounds nor evidence of passage of flatus and stool is required for the initiation of enteral feeding. (Grade: B)

Rationale. The literature supports the concept that bowel sounds and evidence of bowel function (ie, passing flatus or stool) are not required for initiation of enteral feeding. GI dysfunction in the ICU setting occurs in 30%-70% of patients depending on the diagnosis, premorbid condition, ventilation mode, medications, and metabolic state.77

Proposed mechanisms of ICU and postoperative GI dysfunction can be separated into 3 general categories: mucosal barrier disruption, altered motility and atrophy of the mucosa, and reduced mass of GALT.

Bowel sounds are only indicative of contractility and do not necessarily relate to mucosal integrity, barrier function, or absorptive capacity. Success at attaining nutrition goals within the first 72 hours ranges from 30% to 85%. When ICU enteral feeding protocols are followed, rates of GI tolerance in the range of 70%-85% can be achieved.76 Ten randomized clinical trials,63-72 the majority in surgical critically ill patients, have reported feasibility and safety of enteral feeding within the initial 36-48 hours of admission to the ICU. The grade of this recommendation is based on the strength of the literature supporting A3, where patients in the experimental arm of the above mentioned studies were successfully started on EN within the first 36 hours of admission (regardless of clinical signs of stooling, flatus, or borborygmi). See Table 4 . 63-72

A7. Either gastric or small bowel feeding is acceptable in the ICU setting. Critically ill patients should be fed via an enteral access tube placed in the small bowel if at high risk for aspiration or after showing intolerance to gastric feeding. (Grade: C) Withholding of enteral feeding for repeated high gastric residual volumes alone may be sufficient reason to switch to small bowel feeding (the definition for high gastric residual volume is likely to vary from one hospital to the next, as determined by individual institutional protocol). (Grade: E) (See guideline D4 for recommendations on gastric residual volumes, identifying high risk patients, and reducing chances for aspiration.)

Rationale. Multiple studies have evaluated gastric vs jejunal feeding in various medical and surgical ICU settings. One level II study comparing gastric vs jejunal feeding showed significantly less gastroesophageal reflux with small bowel feeding.78 In a nonrandomized prospective study using a radioisotope in an enteral formulation, esophageal reflux was reduced significantly with a trend toward reduced aspiration as the level of infusion was moved from the stomach down through the third portion of the duodenum.79 Three meta-analyses have been published comparing gastric with post-pyloric feeding in the ICU setting.80-82 Only 1 of these meta-analyses showed a significant reduction in ventilator-associated pneumonia with post-pyloric feeding (RR = 0.76; 95% CI 0.59-0.99; P = .04),82 an effect heavily influenced by 1 study by Taylor et al.23 With removal of this study from the meta-analysis, the difference was no longer significant. The 2 other meta-analyses (which did not include the Taylor study) showed no difference in pneumonia between gastric and post-pyloric feeding.80,81 While 1 showed no difference in ICU length of stay,80 all 3 meta-analyses showed no significant difference in mortality between gastric and post-pyloric feeding.80-82 See Table 5 . 23,68,78,83-91

Table 5. Randomized Studies Evaluating Small Bowel (SB) vs Gastric Feeding inCritically Ill Patients
Study Population Study Groups ICU Mortality Pneumonia LOS Days, Mean ± SD (or Range) Other Outcomes Nutrition Outcomes
Montecalvo et al,199283 Level II MICU/SICU (n = 38) Duration MV, mean ± SD % Goal feeds delivered
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,199984 Level II Trauma (n = 80) Duration MV, mean (range) Time to goal feeds
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,199923 Level II Trauma head injury (n = 82) NR NR % Goal feeds delivered
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,200085 Level II MICU (n = 44) NR % Goal feeds delivered
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,200068 Level II Trauma (n = 27) Duration MV, mean ± SD # pts >50% goal × 5 d
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 ± 8.8ICUa
Gastric 11.3 ± 6.1 ICU
Lien et al, 200078Level II Neuro CVA (n = 8) NR NR NR % Time esophageal pH <4 NR
SB 12.9 min (4.9-28.2)
Gastric 24.0 min (19.0-40.6)
Day et al, 200186Level II ICU (n = 25) NR NR NR # tubes replaced
SB 0/14 (0%) 16 per group
Gastric 2/11 (18%) 9 per group
Esparza et al,200187 Level II MICU (n = 54) NR NR NR % Goal feeds delivered
SB 10/27 (37%) 66.0%
Gastric 11/27 (41%) 64.0%
Boivin et al,200188 Level II MICU/SICU/neuro ICU (n = 80) NR NR NR Time to goal feeds
SB 18/39 (46%) 33 h
Gastric 18/39 (46%) 32 h
Neumann et al,200289 Level II MICU (n = 60) NR NR NR Time to goal feeds
SB 1/30 (3%)c 43.0 ± 24.1 h
Gastric 0/30 (0%) 28.8 ± 15.9 h
Davies et al,200290 Level II MICU/SICU (n = 73) NR Time to goal feeds
SB 4/34 (12%) 2/31 (6%) 13.9 ± 1.8ICUa 23.2 ± 3.9 h
Gastric 5/39 (13%) 1/35 (3%) 10.4 ± 1.2 ICU 23.0 ± 3.4 h
Montejo et al,200291 Level I ICU (n = 101) NR % Goal feeds by day 7
SB 19/50 (38%) 16/50 (32%) 15 ± 10 ICU 80% ± 28%
Gastric 22/51 (43%) 20/51 (39%) 18 ± 16 ICU 75% ± 30%
  • SD, standard deviation; NR, not reported; ICU, intensive care unit; MICU,medical ICU; SICU, surgical ICU; MV, mechanical ventilation; Pts, patients;CVA, cerebrovascular accident; Neuro, neurologic; d, day(s); h, hour(s); min,minute(s); mo, month(s). Adapted from the Canadian Clinical PracticeGuidelines.21
  • a P ≤ .05.
  • b Total infections.
  • c Aspiration.

B. When to Use Parenteral Nutrition

B1. If early EN is not feasible or available the first 7 days following admission to the ICU, no nutrition support therapy (ie, STD therapy) should be provided. (Grade: C) In the patient who was previously healthy prior to critical illness with no evidence of protein-calorie malnutrition, use of PN should be reserved and initiated only after the first 7 days of hospitalization (when EN is not available). (Grade: E)

Rationale. These 2 recommendations are the most controversial in these guidelines, are influenced primarily by 2 meta-analyses, and should be interpreted very carefully in application to patient care.24,92 Both meta-analyses compared use of PN with STD therapy (where no nutrition support therapy was provided). In critically ill patients in the absence of pre-existing malnutrition (when EN is not available), Braunschweig et al aggregated 7 studies93-99 and showed that use of STD therapy was associated with significantly reduced infectious morbidity (RR = 0.77; 95% CI 0.65-0.91; P <.05) and a trend toward reduced overall complications (RR = 0.87; 95% CI 0.74-1.03; P not provided) compared to use of PN.24 In the same circumstances (critically ill, no EN available, and no evidence of malnutrition), Heyland et al92 aggregated 4 studies96,97,100,101 and showed a significant increase in mortality with use of PN (RR = 0.1.78; 95% CI 1.11-2.85; P < .05) and a trend toward greater rate of complications (RR = 2.40; 95% CI 0.88-6.58; P not provided), when compared to STD therapy. See Table 6 . 93-129

Table 6. Randomized Studies Evaluating Parenteral Nutrition (PN) vs StandardTherapy (STD)
Study Population Protein Energy Malnutrition Study Groups Timing of PN Complications Hospital Mortality
Williams et al,1976102 Level II Esophagogastric Ca (n = 74) PN Preop 2/10 (20%) 6/38 (16%)
STD 7-10 d 3/9 (33%) 8/36 (22%)
Moghissi et al,1977103 Level II Esophageal Ca (n = 15) PN Preop 0/10 (0%) 0/10 (0%)
STD 5-7 d 1/5 (20%) 0/5 (0%)
Holter et al,197794 Level II GI Ca (n = 56) 100% PN Preop 4/30 (13%) 2/30 (7%)
STD 3 d 5/26 (19%) 2/26 (8%)
Preshaw et al,1979104 Level II Colon Ca (n = 47) PN Preop 8/24 (33%) 0/24 (0%)
STD 1 d 4/23 (17%) 0/23 (0%)
Heatley et al,1979105 Level II Esophagogastric Ca (n = 74) PN Preop 3/38(8%)a , b 6/38 (16%)
STD 7-10 d 11/36 (31%) 8/36 (22%)
Simms et al,1980106 Level II Esophageal Ca (n = 20) PN NR NR 1/10 (10%)
STD 1/10 (10%)
Lim et al, 1981107Level II Esophageal Ca (n = 20) 100% PN Preop 1/10 (10%) 1/10 (10%)
STD 21 d 4/10 (40%) 2/10 (20%)
Thompson et al,198198 Level II GI Ca (n = 21) 100% PN Preop 2/12 (17%) 0/12 (0%)
STD 5-14 d 1/9 (11%) 0/9 (0%)
Sako et al,1981108 Level II Head-neck Ca (n = 66) PN NR 15/30 (50%) 17/34 (50%)
STD 18/32 (56%) 8/32 (25%)
Jensen, 1982109Level II Rectal Ca (n = 20) 100% PN Preop NR 0/10 (0%)
STD 2 d 4/10 (40%)
Moghissi et al,1982110 Level II Esophageal Ca (n = 52) PN Preop 1/25 (4%) 1/25 (4%)
STD 6-8 d 4/27 (15%) 5/27 (19%)
Muller et al,198295/1986111Level I GI Ca (n = 171) 60% PN (gluc) Preop 11/66 (17%)b 3/66 (5%)b
PN (gluc/lipid) 10 d 17/46 (37%) 10/46 (22%)
STD 19/59 (32%) 11/59 (19%)
Garden et al,1983112 Level II Perioperative (n = 20) PN NR 1/10 (10%) 0/10 (0%)
STD 2/10 (20%) 1/10 (10%)
Sax et al, 198797Level II Acute pancreatitis (n = 55) 0% PN NA 4/29 (14%)c 1/29 (3%)
STD 1/26 (4%) 1/26 (4%)
Bellantone et al,1988113 (JPEN)Level II GI Ca (n = 91) 100% PN Preop 12/40 (30%)c 1/40 (3%)
STD ≥7 d 18/51 (35%) 2/51 (4%)
Smith et al,1988114 Level II GI Ca (n = 34) 100% PN Preop 3/17 (18%) 1/17 (6%)
STD 8-15 d 6/17 (35%) 3/17 (18%)
Meguid et al,1988115 Level II GI Ca (n = 66) 100% PN Preop 10/32 (31%)b 1/32 (3%)
STD 8 d 19/34 (56%) 0/34 (0%)
Bellantone et al,1988116 Level I GI Ca (n = 100) PN Preop 8/54(15%)b , c 1/54 (2%)
STD ≥7 d 22/46 (48%) 1/46 (2%)
Fan et al, 1989117Level II Esophageal Ca (n = 40) 75% PN Preop 17/20 (85%) 6/20 (30%)
STD 14 d 15/20 (75%) 6/20 (30%)
VA Co-OP 1991118Level I Perioperative (n = 459) 100% PN Preop 49/192 (26%) 31/231 (13%)
STD 7-15 d 50/203 (25%) 24/228 (11%)
Von Meyenfeldt et al,1992119 Level I Perioperative (n = 101) 29% PN Preop 6/51 (12%) 2/51 (4%)
STD 10-23 d 7/50 (14%) 2/50 (4%)
Fan et al, 1994120Level I Hepatocellular Ca (n = 124) 26% PN Preop 22/64 (34%)b 5/64 (8%)
STD 7 d 33/60 (55%) 9/60 (15%)
Xian-Li et al,2004121 Level II Acute pancreatitis (n = 44) PN NA 11/21 (52%)c 3/21 (14%)
STD 21/23 (91%) 10/23 (44%)
Abel et al,1976100 Level II Perioperative (n = 44) 100% PN Postop 2/20 (10%) 4/20 (20%)
STD 0/24 (0%) 3/24 (13%)
Collins et al,1978122 Level II GI surgery (n = 20) 40% PN Postop 2/10 (20%) 0/10 (0%)
STD 0/10 (0%) 0/10 (0%)
Freund et al,1979123 Level II GI surgery (n = 35) 0% PN Postop 0/25 (0%) 0/25 (0%)
STD 0/10 (0%) 0/10 (0%)
Yamada et al,1983124 Level II GI surgery (n = 57) PN Postop 0/29 (0%) 0/29 (0%)
STD 5/28 (18%) 1/28 (4%)
Jiménez et al,1986125 Level II GI surgery (n = 75) 100% PN Postop 6/60 (10%) 4/60 (7%)
STD 3/15 (20%) 1/15 (7%)
Askanazi et al,1986126 Level II GU surgery (n = 35) PN Postop 1/22 (5%) 0/22 (0%)
STD 2/13 (15%) 2/13 (15%)
Figueras et al,1988127 Level II GI surgery (n = 49) 0% PN Postop 4/25 (16%) 0/25 (0%)
STD 5/24 (21%) 0/24 (0%)
Woolfson et al,198999 Level I Perioperative (n = 122) 0% PN Postop 6/62 (10%) 8/62 (13%)
STD 4/60 (7%) 8/60 (13%)
Reilly et al,1996101 Level II Liver transplant (n = 28) 100% PN Postop NR 0/8 (0%)
PN/BCAA 1/10 (10%)
STD 2/10 (20%)
Gys et al, 1990128Level II GI surgery (n = 20) 0% PN Postop 1/10 (10%) 0/10 (0%)
STD 1/10 (10%) 0/10 (0%)
Sandstrom et al,199396 Level I Surgery, trauma (n = 300) 23% PN Postop NR 12/150 (8%)
STD 10/150 (7%)
Hwang et al,1993129 Level II GI surgery (n = 58) PN Postop 0/26 (0%) 0/26 (0%)
STD 0/32 (0%) 0/32 (0%)
Brennan et al,199493 Level I Pancreatic Ca (n = 117) 100% PN Postop 27/60 (45%) 4/60 (7%)
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). Adapted from Heyland etal,21 Klein etal,131 and withpermission from Braunschweig et al, Am J Clin Nutr. 2001;74:534-542,American Society for Nutrition and Detsky et al, Ann Intern Med.1987;107:195-203,130American College of Physicians.
  • a wound infection.
  • b P < .05.
  • c Infection.

With increased duration of severe illness, priorities between STD therapy and PN become reversed. Sandstrom et al first showed that after the first 14 days of hospitalization had elapsed, continuing to provide no nutrition therapy was associated with significantly greater mortality (21% vs 2%, P < .05) and longer hospital length of stay (36.3 days vs 23.4 days, P < .05), when compared respectively to use of PN.96 The authors of both metaanalyses speculated as to the appropriate length of time before initiating PN in a patient on STD therapy who has not begun to eat spontaneously (Braunschweig recommending 7-10 days, Heyland recommending 14 days).24,92 Conflic ting data were reported in a Chinese study of patients with severe acute pancreatitis. In this study, a significant step-wise improvement was seen in each clinical outcome parameter (hospital length of stay, pancreatic infection, overall complications, and mortality) when comparing patients randomized to STD therapy vs PN vs PN with parenteral glutamine, respectively.121 Because of the discrepancy, we attempted to contact the authors of this latter study to get validation of results but were unsuccessful. The final recommendation was based on the overall negative treatment effect of PN over the first week of hospitalization seen in the 2 metaanalyses.24,92 Although the literature cited recommends withholding PN for 10-14 days, the Guidelines Committee expressed concern that continuing to provide STD therapy (no nutrition support therapy) beyond 7 days would lead to deterioration of nutrition status and an adverse effect on clinical outcome.

B2. If there is evidence of protein-calorie malnutrition on admission and EN is not feasible, it is appropriate to initiate PN as soon as possible following admission and adequate resuscitation. (Grade: C)

Rationale. In the situation where EN is not available and evidence of protein-calorie malnutrition is present (usually defined by recent weight loss of >10%-15% or actual body weight <90% of ideal body weight), initial priorities are reversed and use of PN has a more favorable outcome than STD therapy. See Table 6 . 93-129

In the Heyland meta-analysis, use of PN in malnourished ICU patients was associated with significantly fewer overall complications (RR = 0.52; 95% CI 0.30-0.91; P < .05) than STD therapy.92 In the Braunschweig meta-analysis, STD therapy in malnourished ICU patients was associated with significantly higher risk for mortality (RR = 3.0; 95% CI 1.09-8.56; P < .05) and a trend toward higher rate of infection (RR = 1.17; 95% CI 0.88-1.56; P not provided) compared to use of PN.24 For these patients, when EN is not available, there should be little delay in initiating PN after admission to the ICU.

B3. If a patient is expected to undergo major upper GI surgery and EN is not feasible, PN should be provided under very specific conditions:

  • If the patient is malnourished, PN should be initiated 5-7 days preoperatively and continued into the postoperative period. (Grade: B)

  • PN should not be initiated in the immediate postoperative period but should be delayed for 5-7 days (should EN continue not to be feasible). (Grade: B)

  • PN therapy provided for a duration of <5-7 days would be expected to have no outcome effect and may result in increased risk to the patient. Thus, PN should be initiated only if the duration of therapy is anticipated to be7 days. (Grade: B)

Rationale. One population of patients that has shown more consistent benefit of PN over STD involve those patients undergoing major upper GI surgery (esophagectomy, gastrectomy, pancreatectomy, or other major reoperative abdominal procedures), especially if there is evidence of preexisting protein-calorie malnutrition and the PN is provided under specific conditions.24,92 Whereas critically ill patients in the Heyland meta-analysis experienced increased mortality with use of PN compared to STD therapy (see rationale for guideline B1 above), surgical patients saw no treatment effect with PN regarding mortality (RR = 0.91; 95% CI 0.68-1.21; P = NS).92 Critically ill patients experienced a trend toward increased complications, while surgical patients saw significant reductions in complications with use of PN regarding mortality (RR = 2.40; 95% CI 0.88-6.58; P < .05).92

These benefits were noted when PN was provided preoperatively for a minimum of 7-10 days and then continued through the perioperative period. In an earlier meta-analysis by Detsky et al130 comparing perioperative PN with STD therapy, only seven95,98,102,103,107,110,111 out of 14 studies94,100,104,106,108,109,112 provided PN for ≥7 days.130 As a result, only 1 study showed a treatment effect95 and the overall meta-analysis showed no statistically significant benefit from PN.130 In contrast, a later meta-analysis by Klein et al131 aggregated the data from 13 studies,95,98,103,105,111,113-120 all of which provided PN for ≥7 days.131 Six of the studies showed significant beneficial treatment effects from use of PN,95,103,105,111,115,120 with the pooled data from the overall meta-analysis showing a significant 10% decrease in infectious morbidity compared to STD therapy.131 See Table 6 . 93-129

It is imperative to be aware that the beneficial effect of PN is lost if given only postoperatively. Aggregation of data from 9 studies that evaluated routine postoperative PN93,94,96,99-101,104,109,122 showed a significant 10% increase in complications compared to STD therapy.131 Because of the adverse outcome effect from PN initiated in the immediate postoperative period, Klein et al recommended delaying PN for 5-10 days following surgery if EN continues not to be feasible.131

C. Dosing of Enteral Feeding

C1. The target goal of EN (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy. (Grade: C) Energy requirements may be calculated by predictive equations or measured by indirect calorimetry. Predictive equations should be used with caution, as they provide a less accurate measure of energy requirements than indirect calorimetry in the individual patient. In the obese patient, the predictive equations are even more problematic without availability of indirect calorimetry. (Grade: E)

Rationale. Clinicians should clearly identify the goal of EN, as determined by energy requirements. Over 200 predictive equations (including Harris-Benedict, Scholfield, Ireton-Jones, etc) have been published in the literature.132 Energy requirements may be calculated either through simplistic formulas (25-30 kcal/kg/d), published predictive equations, or the use of indirect calorimetry. Calories provided via infusion of propofol should be considered when calculating the nutrition regimen. While it is often difficult to provide 100% of goal calories by the enteral route, studies in which a protocol was used to increase delivery of EN have shown that delivering a volume of EN where the level of calories and protein provided is closer to goal improves outcome.133,134 This recommendation is supported by two level II studies in which those patients who by protocol randomization received a greater volume of EN experienced significantly fewer complications and less infectious morbidity,23 as well as shorter hospital lengths of stay, and a trend toward lower mortality135 than those patients receiving lower volume.

C2. Efforts to provide >50%-65% of goal calories should be made in order to achieve the clinical benefit of EN over the first week of hospitalization. (Grade: C)

Rationale. The impact of early EN on patient outcome appears to be a dose-dependent effect. “Trickle” or trophic feeds (usually defined as 10-30 mL/h) may be sufficient to prevent mucosal atrophy but may be insufficient to achieve the usual endpoints desired from EN therapy. Studies suggest that >50%-65% of goal calories may be required to prevent increases in intestinal permeability in burn and bone-marrow transplant patients, to promote faster return of cognitive function in head injury patients, and to improve outcome from immune-modulating enteral formulations in critically ill patients.5,23,133,136 This recommendation is supported by one level II23 and one level III study136 where increases in the percent goal calories infused from a range of 37%-40% up to 59%-64% improved clinical outcome.

C3. If unable to meet energy requirements (100% of target goal calories) after 7-10 days by the enteral route alone, consider initiating supplemental PN. (Grade: E) Initiating supplemental PN prior to this 7-10 day period in the patient already receiving EN does not improve outcome and may be detrimental to the patient. (Grade: C)

Rationale. Early on, EN is directed toward maintaining gut integrity, reducing oxidative stress, and modulating systemic immunity. In patients already receiving some volume of EN, use of supplemental PN over the first 7-10 days adds cost137,138 and appears to provide no additional benefit.42,137-140 In 1 small study in burn patients, EN supplemented with PN was associated with a significant increase in mortality (63% vs 26%, P < .05) when compared respectively to hypocaloric EN alone.138 See Table 7 . 42,137-140

Table 7. Randomized Studies Evaluating Enteral Nutrition (EN) vs EN SupplementedWith Parenteral Nutrition (EN+PN) in Critically Ill Patients
Study Population Study Groups Mortality Infections LOS Day(s), Mean ± SD Ventilator Days, Mean ± SD Cost
Herndon et al,1987139 Level II Burn (n = 28) EN+PN 8/13 (62%) ICU NR NR NR NR
EN 8/15 (53%) ICU
Herndon et al,1989140 Level II Burn (n = 39) EN+PN 10/16 (63%) > 14da NR NR NR NR
EN 6/23 (26%) > 14 d
Dunham et al,199442 Level II Trauma (n = 37) EN+PN 3/10 (30%) ICU NR NR NR NR
EN 1/12 (8%) ICU
Chiarelli et al,1996137 Level II ICU (n = 24) EN+PN 3/12 (25%) ICU 6/12 (50%) 37 ± 13 Hosp 19 ± 6 EN+PN 50,000a
EN 4/12 (33%) ICU 3/12 (25%) 41 ± 23 Hosp 19 ± 2 lira/yr more than EN
Bauer et al,2000138 Level I ICU (n = 120) EN+PN 3/60 (5%) at 4 d 39/60 (65%) 31.2 ± 18.5 Hosp 11 ± 9 204 ± 119Euros/pta
EN 4/60 (7%) at 4 d 39/60 (65%) 33.7 ± 27.7 Hosp 10 ± 8
EN+PN 17/60 (28%) at 90 d 16.9 ± 11.8 ICU 106 ± 47 Euros/pt
EN 18/60 (30%) at 90 d 17.3 ± 12.8 ICU
  • SD, standard deviation; NR, not reported; ICU, intensive care unit; Hosp,hospital; LOS, length of stay; pt, patient; d, day(s); yr, year(s) Adapted from the Canadian Clinical PracticeGuidelines.21
  • a P ≤ .05.

As discussed in guideline B1, the optimal time to initiate PN in a patient who is already receiving some volume of enteral feeding is not clear. The reports by Braunschweig et al and Sandstrom et al infer that after the first 7-10 days, the need to provide adequate calories and protein is increased in order to prevent the consequences of deterioration of nutrition status.24,96 At this point, if the provision of EN is insufficient to meet requirements, then the addition of supplemental PN should be considered.

C4. Ongoing assessment of adequacy of protein provision should be performed. The use of additional modular protein supplements is a common practice, as standard enteral formulations tend to have a high non-protein calorie:nitrogen ratio. In patients with body mass index (BMI) <30, protein requirements should be in the range of 1.2-2.0 g/kg actual body weight per day, and may likely be even higher in burn or multi-trauma patients. (Grade: E)

Rationale. In the critical care setting, protein appears to be the most important macronutrient for healing wounds, supporting immune function, and maintaining lean body mass. For most critically ill patients, protein requirements are proportionately higher than energy requirements and therefore are not met by provision of routine enteral formulations. The decision to add protein modules should be based on an ongoing assessment of adequacy of protein provision. Unfortunately in the critical care setting, determination of protein requirements is difficult but may be derived with limitations from nitrogen balance, simplistic equations (1.2-2.0 g/kg/d) or non-protein calorie:nitrogen ratio (70:1-100:1). Serum protein markers (albumin, prealbumin, transferrin, C-reactive protein) are not validated for determining adequacy of protein provision and should not be used in the critical care setting in this manner.141

C5. In the critically ill obese patient, permissive underfeeding or hypocaloric feeding with EN is recommended. For all classes of obesity where BMI is >30, the goal of the EN regimen should not exceed 60%-70% of target energy requirements or 11-14 kcal/kg actual body weight per day (or 22-25 kcal/kg ideal body weight per day). Protein should be provided in a range2.0 g/kg ideal body weight per day for Class I and II patients (BMI 30-40),2.5 g/kg ideal body weight per day for Class III (BMI40). Determining energy requirements is discussed in guideline C1. (Grade: D)

Rationale. Severe obesity adversely affects patient care in the ICU and increases risk of comorbidities (eg, insulin resistance, sepsis, infections, deep venous thrombosis, organ failure).142,143 Achieving some degree of weight loss may increase insulin sensitivity, improve nursing care, and reduce risk of comorbidities. Providing 60%-70% of caloric requirements promotes steady weight loss, while infusing protein at a dose of 2.0-2.5 g/kg ideal body weight per day should approximate protein requirements and neutral nitrogen balance, allowing for adequate wound healing.142 A retrospective study by Choban and Dickerson indicated that provision of protein at a dose of 2.0 g/kg ideal body weight per day is insufficient for achieving neutral nitrogen balance when the BMI is> 40.142 Use of BMI and ideal body weight is recommended over use of adjusted body weight.

D. Monitoring Tolerance and Adequacy of Enteral Nutrition

D1. In the ICU setting, evidence of bowel motility (resolution of clinical ileus) is not required in order to initiate EN in the ICU. (Grade: E)

Rationale. Feeding into the GI tract is safe prior to the emergence of overt evidence of enteric function, such as bowel sounds or the passage of flatus and stool. EN promotes gut motility. As long as the patient remains hemodynamically stable, it is safe and appropriate to feed through mild to moderate ileus.2

D2. Patients should be monitored for tolerance of EN (determined by patient complaints of pain and/or distention, physical exam, passage of flatus and stool, abdominal radiographs). (Grade: E) Inappropriate cessation of EN should be avoided. (Grade: E) Holding EN for gastric residual volumes<500 mL in the absence of other signs of intolerance should be avoided. (Grade: B) The time period that a patient is made nil per os (NPO) prior to, during, and immediately following the time of diagnostic tests or procedures should be minimized to prevent inadequate delivery of nutrients and prolonged periods of ileus. Ileus may be propagated by NPO status. (Grade: C)

Rationale. A number of factors impede the delivery of EN in the critical care setting.144 Healthcare providers who prescribe nutrition formulations tend to under-order calories, and thus patients only receive approximately 80% of what is ordered. This combination of under-ordering and inadequate delivery results in patients receiving only 50% of target goal calories from one day to the next. Cessation of feeding occurs in >85% of patients for an average of 20% of the infusion time (the reasons for which are avoidable in >65% of occasions).144 Patient intolerance accounts for one-third of cessation time, but only half of this represents true intolerance. Other reasons for cessation include remaining NPO after midnight for diagnostic tests and procedures in another third of patients, with the rest being accounted for by elevated gastric residual volumes and tube displacement.144 In one level II study, patients randomized to continue EN during frequent surgical procedures (burn wound debridement under general anesthesia) had significantly fewer infections than those patients for whom EN was stopped for each procedure.145

Gastric residual volumes do not correlate well to incidence of pneumonia,23,146,147 measures of gastric emptying,148-150 or to incidence of regurgitation and aspiration.151 Four level II studies indicate that raising the cutoff value for gastric residual volume (leading to automatic cessation of EN) from a lower number of 50-150 mL to a higher number of 250-500 mL does not increase risk for regurgitation, aspiration, or pneumonia.23,146,147,151 Decreasing the cutoff value for gastric residual volume does not protect the patient from these complications, often leads to inappropriate cessation, and may adversely affect outcome through reduced volume of EN infused.23 Gastric residual volumes in the range of 200-500 mL should raise concern and lead to the implementation of measures to reduce risk of aspiration, but automatic cessation of feeding should not occur for gastric residual volumes <500 mL in the absence of other signs of intolerance.152 See Table 8 . 23,146,147,151

Table 8. Randomized Studies Evaluating Lower vs Higher “CutoffValues” for Gastric Residual Volumes (GRVs)
Study Population Study Groups byGRVsa % Goal kcal Infused Mean ± SD Pneumonia Aspiration Mean ± SD GI Intolerance Mean ± SD Other
Taylor et al,199923 Level II Trauma, head injury (n = 82) NR NR Infection
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 Level II ICU (n = 80) NR ICU LOS
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,2005151 Level II ICU (n = 40) 200 mL 77.0% ± 21.2% NR 21.6% ±25.6%d 35.0% ±27.3%e
400 mL 77.8% ± 32.5% 22.6% ± 25.0% 27.8% ± 25.0%
Montejo et al,2008147 Level I ICU (n = 329) 200 mL 82.8% ±1.7%f 46/169 (27%) NR 107/169 (64%)
500 mL 89.6% ±1.8%c 45/160 (28%) 76/160 (48%)c
  • 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 4hours.
  • e Incidence of regurgitation as a percentage of all bedside checks done every4 hours.
  • f Percentage goal feeding on day 3 (similar to significant differences on day7).

D3. Use of enteral feeding protocols increases the overall percentage of goal calories provided and should be implemented. (Grade: C)

Rationale. Use of ICU or nurse-driven protocols which define goal infusion rate, designate more rapid startups, and provide specific orders for handling gastric residual volumes, frequency of flushes, and conditions or problems under which feeding may be adjusted or stopped, have been shown to be successful in increasing the overall percentage of goal calories provided.23,76,133,135,153,154

D4. Patients placed on EN should be assessed for risk of aspiration. (Grade: E) Steps to reduce risk of aspiration should be employed. (Grade: E)

The following measures have been shown to reduce risk of aspiration:

  • In all intubated ICU patients receiving EN, the head of the bed should be elevated 30°-45°. (Grade: C)

  • For high-risk patients or those shown to be intolerant to gastric feeding, delivery of EN should be switched to continuous infusion. (Grade: D)

  • Agents to promote motility such as prokinetic drugs (metoclopramide and erythromycin) or narcotic antagonists (naloxone and alvimopan) should be initiated where clinically feasible. (Grade: C)

  • Diverting the level of feeding by post-pyloric tube placement should be considered. (Grade: C)

  • Use of chlorhexidine mouthwash twice a day should be considered to reduce risk of ventilator-associated pneumonia. (Grade: C)

Rationale. Aspiration is one of the most feared complications of EN. Patients at increased risk for aspiration may be identified by a number of factors, including use of a nasoenteric tube, an endotracheal tube and mechanical ventilation, age >70 years, reduced level of consciousness, poor nursing care, location in the hospital, patient position, transport out of the ICU, poor oral health, and use of bolus intermittent feedings.152 Pneumonia and bacterial colonization of the upper respiratory tree are more closely associated with aspiration of contaminated oropharyngeal secretions than regurgitation and aspiration of contaminated gastric contents.155-157

Several methods may be used to reduce the risk of aspiration. As mentioned in guideline A6, changing the level of infusion of EN from the stomach to the small bowel has been shown to reduce the incidence of regurgitation and aspiration,78,79 although the results from 3 meta-analyses (as discussed under guideline A6) suggest that any effect in reducing pneumonia is minimal.80-82 See Table 5 . 23,68,78,83-91

Elevating the head of the bed 30°-45° was shown in 1 study to reduce the incidence of pneumonia from 23% to 5%, comparing supine to semi-recumbent position, respectively (P = .018).158 See Table 9 . 158,159

Table 9. Randomized Studies Evaluating Body Position During Tube Feeding inCritically Ill Patients, Supine vs Semirecumbent
Study Population Study Groups Mortality Pneumonia Hospital LOS Days, Mean ± SD (or Range) Ventilator Days, Mean ± SD (or Range)
Drakulovic et al,1999158 Level II ICU (n = 90) Semi-rec 7/39 (18%) ICU 2/39 (5%)a 9.7 ± 7.8 ICU 7.1 ± 6.9
Supine 13/47 (28%) ICU 11/47 (23%) 9.3 ± 7.2 ICU 6.0 ± 6.2
van Nieuwenhoven et al,2006159 Level I ICU (n = 221) Semi-rec 33/112 (29%) ICU 13/112 (12%) 27 (2-301) Hosp 6 (0-64)
Supine 33/109 (30%) ICU 8/109 (7%) 24 (0-186) Hosp 6 (0-281)
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. Adapted from the Canadian Clinical PracticeGuidelines.21
  • a P ≤ .05.

The potential harm from aggressive bolus infusion of EN leading to increased risk of aspiration pneumonia was shown in 1 study.160 Level II studies comparing bolus to continuous infusion have shown greater volume with fewer interruptions in delivery of EN with continuous feeding but no significant difference between techniques with regard to patient outcome.161,162 See Table 10 . 161-165

Table 10. Randomized Studies Evaluating Continuous vs Bolus Delivery of EnteralNutrition (EN)
Study Population Study Groups Infection Difference in Feeding ICU Mortality Other
Hiebert et al,1981163 Level II Burn (n = 76) NR Time to goal calories Diarrhea (stool frequency)
Continuous 3.1 ± 0.7da 1.8 ±0.4a
Bolus 5.2 ± 0.8 d 3.3 ± 0.7
Kocan et al,1986164 Level II Neuro ICU (n = 34) NR % Goal calories infused NR Aspiration (blue food coloring)
Continuous 62.2% 1/17 (6%)
Bolus 55.9% 3/17 (18%)
Ciocon et al,1992165 Level II Hospitalized dysphagia (n = 60) Daily caloric deficit NR Clogged tube
Continuous 5/30 (17%)b 783 ± 29 kcal/d 15/30 (50%)a
Bolus 10/30 (33%) 795 ± 25 kcal/d 5/30 (17%)
Diarrhea
Continuous 20/30 (67%)a
Bolus 29/30 (97%)
Bonten et al,1996161 Level II ICU (n = 60) Interrupted EN Mortality
Continuous 5/30 (17%) 2/30 (7%) 6/30 (20%) 6/30 (20%)
Bolusc 5/30 (17%) 5/30 (17%) 9/30 (30%) 9/30 (30%)
Steevens et al,2002162 Level II Trauma ICU (n = 18) Interrupted EN NR
Continuous 0/9 (0%)b 3/9 (33%)
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.

Adding prokinetic agents such as erythromycin or metoclopramide has been shown to improve gastric emptying and tolerance of EN but has resulted in little change in clinical outcome for ICU patients.166 See Table 11 . 167-169 Use of naloxone infused through the feeding tube (to reverse the effects of opioid narcotics at the level of the gut in order to improve intestinal motility) was shown in one level II study to significantly increase the volume of EN infused, reduce gastric residual volumes, and decrease the incidence of ventilator-associated pneumonia (compared to placebo).169

Table 11. Randomized Studies With vs Without Motility Agents in Critically IllPatients
Study Population Study Groups ICU Mortality Pneumonia Nutrition Outcomes
Yavagal et al,2000167 Level I ICU (n = 305) Metoclopramide 10 mg NG 73/131 (56%) 22/131 (17%) NR
Placebo 92/174 (53%) 24/174 (14%)
Berne et al,2002168 Level II Trauma (n = 48) EN tolerated at 48 h
Erythromycin 250 mg IV q 6 h 2/32 (6%) 13/32 (40%) 58%
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,2003169 Level II ICU (n = 84) Mean GRV
Naloxone 8 mg q 6 h NG 6/38 (16%) 13/38 (34%)a 54 mL
Placebo 7/43 (16%) 24/43 (56%) 129 mL
Volume EN delivered was higher after day 3 in Naloxone group compared tocontrols (trend)
  • NR, not reported; ICU, intensive care unit; GRV, gastric residual volume;IV, intravenous; NG, nasogastric; EN, enteral nutrition; h, hour(s). Adapted from the Canadian Clinical PracticeGuidelines.21
  • a P ≤ .05.

Optimizing oral health with chlorhexidine mouthwashes twice daily was shown in 2 studies to reduce respiratory infection and nosocomial pneumonia in patients undergoing heart surgery.170,171 While studies evaluating use of chlorhexidine in general ICU populations have shown little outcome effect, 2 studies in which chlorhexidine oral care was included in bundled interventions showed significant reductions in nosocomial respiratory infections.172,173 Other steps to decrease aspiration risk would include reducing the level of sedation/analgesia when possible, minimizing transport out of the ICU for diagnostic tests and procedures, and moving the patient to a unit with a lower patient:nurse ratio.152,174

D5. Blue food coloring and glucose oxidase strips, as surrogate markers for aspiration, should not be used in the critical care setting. (Grade: E)

Rationale. Traditional monitors for aspiration are ineffective. Blue food coloring, an insensitive marker for aspiration, was shown to be associated with mitochondrial toxicity and patient death.175 The United States Food and Drug Administration through a Health Advisory Bulletin (September 2003) issued a mandate against the use of blue food coloring as a monitor for aspiration in patients on EN.176 The basic premise for use of glucose oxidase (that glucose content in tracheal secretions is solely related to aspiration of glucose-containing formulation) has been shown to be invalid, and its use is thwarted by poor sensitivity/specificity characteristics.177

D6. Development of diarrhea associated with enteral tube feedings warrants further evaluation for etiology. (Grade: E)

Rationale. Diarrhea in the ICU patient receiving EN should prompt an investigation for excessive intake of hyperosmolar medications, such as sorbitol, use of broad spectrum antibiotics, Clostridium difficile pseudomembranous colitis, or other infectious etiologies. Most episodes of nosocomial diarrhea are mild and self-limiting.178

Assessment should include an abdominal exam, fecal leukocytes, quantification of stool, stool culture for C. difficile (and/or toxin assay), serum electrolyte panel (to evaluate for excessive electrolyte losses or dehydration), and review of medications. An attempt should be made to distinguish infectious diarrhea from osmotic diarrhea.179

E. Selection of Appropriate Enteral Formulation

E1. Immune-modulating enteral formulations (supplemented with agents such as arginine, glutamine, nucleic acid, ω-3 fatty acids, and antioxidants) should be used for the appropriate patient population (major elective surgery, trauma, burns, head and neck cancer, and critically ill patients on mechanical ventilation), with caution in patients with severe sepsis. (For surgical ICU patients, Grade: A) (For medical ICU patients, Grade: B)

ICU patients not meeting criteria for immune-modulating formulations should receive standard enteral formulations. (Grade: B)

Rationale. In selecting the appropriate enteral formulation for the critically ill patient, the clinician must first decide if the patient is a candidate for a specialty immune-modulating formulation.180 Patients most likely to show a favorable outcome, who thus would be appropriate candidates for use of immune-modulating formulations, include those undergoing major elective GI surgery, trauma (abdominal trauma index scores >20), burns (total body surface area >30%), head and neck cancer, and critically ill patients on mechanical ventilation (who are not severely septic).180

A large body of data suggest that adding pharmaconutrients to enteral formulations provides even further benefits on patient outcome than use of standard formulations alone.181-183 See Table 12 . 184-204 Studies from basic science have provided a rationale for the mechanism of the beneficial effects seen clinically. Such findings include the discovery of specialized immune (myeloid suppressor) cells, whose role is to regulate the availability of arginine, necessary for normal T lymphocyte function. These myeloid suppressor cells are capable of causing states of severe arginine deficiency which impact production of nitric oxide and negatively affect microcirculation. Immune-modulating diets containing arginine and ω-3 fatty acids appear to overcome the regulatory effect of myeloid suppressor cells.205 Agents such as RNA nucleotides increase total lymphocyte count, lymphocyte proliferation, and thymus function. In a dynamic fashion, the ω-3 fatty acids eicosapentaenoic acid (EPA) and docosohexaenoic acid (DHA) displaceω -6 fatty acids from the cell membranes of immune cells. This effect reduces systemic inflammation through the production of alternative biologically less active prostaglandins and leukotrienes. EPA and DHA (fish oils) have also been shown to down-regulate expression of nuclear factor-kappa B (NFκB), intracellular adhesion molecule 1 (ICAM-1), and E-selectin, which in effect decreases neutrophil attachment and transepithelial migration to modulate systemic and local inflammation. In addition, EPA and DHA help to stabilize the myocardium and lower the incidence of cardiac arrhythmias, decrease incidence of acute respiratory distress syndrome (ARDS), and reduce the likelihood of sepsis.206-209 Glutamine, considered a conditionally essen tial amino acid, exerts a myriad of beneficial effects on antioxidant defenses, immune function, production of heat shock proteins, and nitrogen retention. Addition of agents such as selenium, ascorbic acid (vitamin C), and vitamin E provides further antioxidant protection.

Table 12. Immune-Modulating Enteral Nutrition (EN) vs Standard EN (Stand EN) inCritically Ill Patients
Study Population Study Groups Mortality Infectionsa LOS Days, Mean ± SD (or Range) Ventilator Days, Mean ± SD (or Range)
Cerra et al,1990184 Level II Surgical ICU (n = 20) Impactb 1/11 (9%) ICU NR 36.7 ± 8.5Hospc NR
Osmolite HN 1/9 (11%) ICU 54.7 ± 10.5 Hosp
Gottschlich et al,1990185 Level II Critically ill burns (n = 31) Shriners burnformulad 2/17 (12%) ICU NR NR 9 ± 4.5
Osmolite HN + protein 1/14 (7%) ICU 10 ± 2.5
Brown et al,1994186 Level II Trauma (n = 37) Experimentalformulad 0/19 (0%) ICU 3/19 (16%)c NR NR
Osmolite HN + protein 0/18 (0%) ICU 10/18 (56%)
Moore et al,1994187 Level II Trauma (n = 98) Immun-Aidb 1/51 (2%) ICU 9/51 (18%) 14.6 ± 1.3Hospc 1.9 ±0.9c
Vivonex TEN 2/47 (4%) ICU 10/47 (21%) 17.2 ± 2.8 Hosp 5.3 ± 3.1
Immun-Aidb 5.3 ± 0.8ICUc
Vivonex TEN 8.6 ± 3.1 ICU
Bower et al,1995188 Level I ICU (n = 296) Impactd 24/153 (16%) ICU 86/153 (56%) 27.6 ± 23 Hosp NR
Osmolite 12/143 (8%) ICU 90/143 (63%) 30.9 ± 26 Hosp
Kudsk et al,1996189 Level II Trauma (n = 35) Immun-Aidb 1/17 (6%) ICU 5/16 (31%) 18.3 ± 2.8Hospc 2.4 ±1.3c
Stand EN 1/18 (6%) ICU 11/17 (65%) 32.6 ± 7.0 Hosp 5.4 ± 2.0
Immun-Aidb 5.8 ± 1.8ICUc
Stand EN 9.5 ± 2.3 ICU
Engel et al,1997190 Level II Trauma (n = 36) Impactb 7/18 (39%) ICU 6/18 (33%) 19.0 ± 7.4 ICU 14.8 ± 5.6
Stand EN 5/18 (28%) ICU 5/18 (28%) 20.5 ± 5.3 ICU 16.0 ± 5.6
Mendez et al,1997191 Level II Trauma (n = 43) Experimentalformulad 1/22 (5%) ICU 19/22 (86%)c 34.0 ± 21.2Hospc 16.5 ± 19.4
Osmolite HN + protein 1/21 (5%) ICU 12/21 (57%) 21.9 ± 11.0 Hosp 9.3 ± 6.0
Experimentalformulad 18.9 ± 20.7 ICU
Osmolite HN + protein 11.1 ± 6.7 ICU
Rodrigo et al,1997192 Level II Mixed ICU (n = 30) Impactd 2/16 (13%) ICU 5/16 (31%) 8.0 ± 7.3 ICU NR
Stand EN 1/14 (7%) ICU 3/14 (21%) 10.0 ± 2.7 ICU
Saffle et al,1997193 Level II Burns (n = 50) Impactd 5/25 (20%) ICU 2.36 per patient 37 ± 4 Hosp 22 ± 3
Replete 3/24 (13%) ICU 1.71 per patient 38 ± 4 Hosp 21 ± 2
Weimann et al,1998194 Level II Trauma (n = 29) Impactd 2/16 (13%) ICU NR 70.2 ± 53 Hosp 21.4 ± 10.8
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 Level I Mixed ICU (n = 390) Impactd 95/197 (48%) ICU 10.5 ± 13.1 ICU 8.0 ± 11.1
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 Level I Critically ill septic (n = 176) Impactd 17/89 (19%)ICUc 39/89 (44%) 18.2 ± 12.6 ICU 16.6 ± 12.9 ICU 12.4 ± 10.4
Stand EN 28/87 (32%) ICU 44/87 (51%) 12.2 ± 10.3
Caparros et al,2001197 Level I ICU patients (n = 235) Experimentalformulab 27/130 (21%) ICU 64/130 (49%)c 15 (10-25) ICU 10 (5-18)
Stand EN 30/105 (29%) ICU 37/105 (35%) 13 (9-20) ICU 9 (5-14)
Experimentalformulab 29 (17-51) Hosp
Stand EN 26 (18-42) Hosp
Conejero et al,2002198 Level II SIRS pts (n = 84) Experimentalformulab 14/47 (30%) at 28 d 11/47 (23%)c 14 (4-63) Hosp 14 (5-25)
Stand EN 9/37 (24%) at 28 d 17/37 (46%) 15 (4-102) Hosp 14 (5-29)
Dent et al,2003199 Level I ICU (n = 170) Optimentalb 20/87 (23%)ICUc 57/87 (66%) 14.8 ± 19.6 ICU 14.3 ± 22.4
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 Level II Severe sepsis (n = 39) Perativee 8/18 (44%) ICU NR 13.5 (9-26) Hosp NR
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 Level II Trauma burns (n = 36) Neoimmuneg 1/18 (6%) ICU NR 3.4 ± 5.8 ICU 2.7 ± 5.2
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 Level II Trauma (n = 25) Stand EN +arginined 1/13 (8%) ICU 8/13 (62%) 13 ± 6 ICU 10 ± 5
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 Level I ICU (n = 597) Stressonf 84/302 (28%) ICU 130/302 (43%) 7 (4-14) ICU 6 (3-12)
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 Level II Burn (n = 23) Cruciald 2/12 (17%) ICU 9/12 (75%) NR NR
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 responsesyndrome. Impact, Vivonex TEN, Replete, Traumacal (Stand EN), and Crucial are allproducts of Nestle Nutrition U.S., Minneapolis, MN; Osmolite HN, Optimental,and Perative are all products of Abbott Laboratories, Columbus, OH; Immun-Aidis a product of B.Braun/McGaw, Irvine, CA; and Stresson is a product ofNutricia Clinical Care, Trowbridge, Wiltshire, Great Britain.
  • a All infections represent number of patients per group with infection unlessotherwise stated.
  • b Non-isonitrogenous.
  • c P ≤ .05.
  • d Isonitrogenous.
  • e Non-isocaloric.
  • f Isocaloric but non-isonitrogenous.
  • g Non-isocaloric and non-isonitrogenous.

Multiple meta-analyses181,182,210-212 have shown that use of immune-modulating formulations is associated with significant reductions in duration of mechanical ventilation, infectious morbidity, and hospital length of stay compared to use of standard enteral formulations. These same 5 meta-analyses showed no overall impact on mortality from use of immune-modulating formulations. See Table 13 . 181,182,210-212 The beneficial outcome effects of the immune-modulating formulations are more uniformly seen in patients undergoing major surgery than in critically ill patients on mechanical ventilation. This influence is even more pronounced when the formulation is given in the preoperative period. By differentiating studies done in surgical ICUs from those done in medical ICUs, Heyland et al showed that the greatest beneficial effect was seen in surgery patients with significant reductions in infectious morbidity (RR = 0.53; 95% CI 0.42-0.68; P ≤ .05) and hospital length of stay (WMD = –0.76; 95% CI– 1.14 to –0.37; P < .05).210 In contrast, aggregating the data from studies in medical ICU patients showed no effect on infections (RR = 0.96; 95% CI 0.77-1.20; P = NS) but a similar reduction in hospital length of stay (WMD = –0.47; 95% CI– 0.93 to –0.01; P = .047).210

Table 13. Meta-Analyses Reported Comparing Immune-Modulating Enteral Formulationsto Standard Enteral Formulations
Author Population No. of Studies Included General Conclusions (Effect of Immune-Modulating vs Standard EnteralFormulations)
Heys et al,1999181 Medical, surgical critical illness, cancer (n = 1009) 11 Decreased infection (OR = 0.47, 95% CI 0.32-0.70, P < .05)
Decreased length of stay (WMD = 2.5, 95% CI 4.0-1.0, P < .05)
No change in mortality (OR = 1.77, 95% CI 1.00-3.12, P = NS)
Beale et al,1999182 Medical, surgical trauma, sepsis, major surgery (n = 1482) 12 Decreased infection (RR = 0.67, 95% CI 0.50-0.89, P = .006)
Decreased ventilator days (WMD = 2.6, 95% CI 0.1-5.1, P = .04)
Decreased length of stay (WMD = 2.9, 95% CI 1.4-4.4, P = .0002)
No change in mortality (RR = 1.05, 95% CI 0.78-1.41, P = NS)
Heyland et al,2001210 Medical, surgical critical illness, major surgery (n = 2419) 22 Decreased infection (RR = 0.66, 95% CI 0.54-0.80, P < .05)
Decreased length of stay (WMD = 3.33, 95% CI 5.63-1.02, P < .05)
No change in mortality (RR = 1.10, 95% CI 0.93-1.31, P = NS)
Montejo et al,2003211 Critical illness (n = 1270) 26 Decreased abdominal abscess (OR = 0.26, 95% CI 0.12-0.55, P = .005)
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 (n = 2305) 17 Decreased infection (RR = 0.49, 95% CI 0.42-0.58, P > .0001)
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.

It has been hypothesized that there may be some increased risk with the use of arginine-containing formulations in medical ICU patients who are severely septic.213,214 Based on one level I report,188 one prospective randomized unblinded study using a control group receiving PN,200 and a third study published in abstract form only,199 use of arginine-containing formulations resulted in greater mortality than standard EN and PN formulations. Two of the 3 studies reporting a potential adverse effect had comparatively lower levels of arginine supplementation.199,200 The mechanism proposed for this adverse effect was that in severe sepsis, arginine may be converted to nitric oxide contributing to hemodynamic instability. This concept is contradicted by 4 other reports. One of these studies showed that infusion of arginine directly into the venous circulation of septic medical and surgical ICU patients caused no hemodynamic stability.215 Three other studies showed that clinical outcome was better195,197 and mortality was reduced in moderately septic ICU patients196 with use of an arginine-containing formulation (compared to a standard enteral formulation). Upon review of this controversy, the Guidelines Committee felt that immune-modulating formulations containing arginine were safe enough to use in mild to moderate sepsis, but that caution should be employed if utilized in patients with severe sepsis.

Unfortunately, few studies have addressed the individual pharmaconutrients, their specific effects, or their proper dosing. This body of literature has been criticized for the heterogeneity of studies, performed in a wide range of ICU patient populations, with a variety of experimental and commercial formulations. Multiple enteral formulations are marketed as being immune-modulating, but vary considerably in their makeup and dosage of individual components. It is not clear whether the data from published studies and these subsequent recommendations can be extrapolated to use of formulations that have not been formally evaluated. Based on the strength and uniformity of the data in surgery patients, the Guidelines Committee felt that a grade A recommendation was warranted for use of these formulations in the surgical ICU. The reduced signal strength and heterogeneity of the data in nonoperative critically ill patients in a medical ICU was felt to warrant a grade B recommendation.

For any patient who does not meet the criteria mentioned above, there is a decreased likelihood that use of immune-modulating formulations will change outcome. In this situation, the added cost of these specialty formulations cannot be justified and therefore standard enteral formulations should be used.180

E2. Patients with ARDS and severe acute lung injury (ALI) should be placed on an enteral formulation characterized by an anti-inflammatory lipid profile (ie, ω-3 fish oils, borage oil) and antioxidants. (Grade: A)

Rationale. In three level I studies involving patients with ARDS, ALI, and sepsis, use of an enteral formulation fortified with ω-3 fatty acids (in the form of EPA), borage oil (γ-linolenic acid [GLA]), and antioxidants was shown to significantly reduce length of stay in the ICU, duration of mechanical ventilation, organ failure, and mortality compared to use of a standard enteral formulation.207-209 Controversy remains as to the optimal dosage, makeup of fatty acids, and ratio of individual immune-modulating nutrients which comprise these formulations. See Table 14 . 207-209

Table 14. Anti-inflammatory Immune-Modulating Enteral Nutrition (Oxepa) vsStandard Enteral Nutrition (Stand EN) in Patients With Acute RespiratoryDistress Syndrome (ARDS), Acute Lung Injury (ALI), and Sepsis
Study Population Study Groups Mortality LOS Days, Mean ± SD Ventilator Days, Mean ± SD New Organ Dysfunction
Gadek et al,1999207 Level I ARDS ICU (n = 146) Oxepa 11/70 (16%) ICU 11.0 ± 0.9ICUa 9.6 ±0.9a 7/70 (10%)a
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 Level I ARDS and ALI (n = 100) Oxepa 14/46 (30%) at 28da 13.5 ± 11.8 ICU 12.1 ± 11.3 NR
Stand EN 26/49 (53%) at 28 d 15.6 ± 11.8 ICU 14.7 ± 12.0
Pontes-Arruda et al,2006209 Level I Severe sepsis ICU (n = 165) Oxepa 26/83 (31%) at 28da 17.2 ± 4.9ICUa 14.6 ±4.3a 32/83 (39%)a
Stand EN 38/82 (46%) at 28 d 23.4 ± 3.5 ICU 22.2 ± 5.1 66/82 (80%)
  • SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS,length of stay; d, day(s). Oxepa: Abbott Nutrition; Columbus, OH.
  • a P ≤ .05.

E3. To receive optimal therapeutic benefit from the immune-modulating formulations, at least 50%-65% of goal energy requirements should be delivered. (Grade: C)

Rationale. The benefit of EN in general,5,23,136 and specifically the added value of immune-modulating agents,182,188,195 appears to be a dose-dependent effect. Significant differences in outcome are more likely to be seen between groups randomized to either an immune-modulating or a standard enteral formulation in those patients who receive a “sufficient” volume of feeding.188,195 These differences may not be as apparent when all patients who receive any volume of feeding are included in the analysis.195

E4. If there is evidence of diarrhea, soluble fiber-containing or small peptide formulations may be utilized. (Grade: E)

Rationale. Those patients with persistent diarrhea (in whom hyperosmolar agents and C. difficile have been excluded) may benefit from use of a soluble fiber-containing formulation or small peptide semi-elemental formulation. The laboratory data, theoretical concepts, and expert opinions would support the use of the small peptide enteral formulations but current large prospective trials are not available to make this a strong recommendation.216

F. Adjunctive Therapy

F1. Administration of probiotic agents has been shown to improve outcome (most consistently by decreasing infection) in specific critically ill patient populations involving transplantation, major abdominal surgery, and severe trauma. (Grade: C) No recommendation can currently be made for use of probiotics in the general ICU population due to a lack of consistent outcome effect. It appears that each species may have different effects and variable impact on patient outcome, making it difficult to make broad categorical recommendations. Similarly, no recommendation can currently be made for use of probiotics in patients with severe acute necrotizing pancreatitis, based on the disparity of evidence in the literature and the heterogeneity of the bacterial strains utilized.

Rationale. Probiotics are defined as microorganisms of human origin, which are safe, stable in the presence of gastric acid and bile salts, and when administered in adequate amounts confer a health benefit to the host. Multiple factors in the ICU induce rapid and persistent changes in the commensal microbiota, including broad spectrum antibiotics, prophylaxis for stress gastropathy, vasoactive pressor agents, alterations in motility, and decreases in luminal nutrient delivery.217,218 These agents act by competitively inhibiting pathogenic bacterial growth, blocking epithelial attachment of invasive pathogens, eliminating pathogenic toxins, enhancing mucosal barrier, and favorably modulating the host inflammatory response.219-221 Unfortunately for the general ICU patient population, there has not been a consistent outcome benefit demonstrated. The most consistent beneficial effect from use of probiotics has been a reduction in infectious morbidity demonstrated in critically ill patients involving transplantation,222,223 major abdominal surgery,224 and trauma.225,226 While some of these studies would warrant a grade B recommendation, the Guidelines Committee felt that the heterogeneity of the ICU populations studied, the difference in bacterial strains, and the variability in dosing necessitated a downgrade to a grade C recommendation. As the ease and reliability of taxonomic classification improve, stronger recommendations for use in specific populations of critically ill patients would be expected.222,224 Probiotics in severe acute pancreatitis are currently under scrutiny due to the results of two level II single center studies showing clinical benefit (significantly reduced infectious morbidity and hospital length of stay),227,228 followed by a larger level I multicenter study showing increased mortality in those patients receiving probiotics.229

F2. A combination of antioxidant vitamins and trace minerals (specifically including selenium) should be provided to all critically ill patients receiving specialized nutrition therapy. (Grade: B)

Rationale. Antioxidant vitamins (including vitamins E and ascorbic acid) and trace minerals (including selenium, zinc, and copper) may improve patient outcome, especially in burns, trauma, and critical illness requiring mechanical ventilation.230,231 A meta-analysis aggregating data from studies evaluating various combinations of antioxidant vitamins and trace elements showed a significant reduction in mortality with their use (RR = 0.65; 95% CI 0.44-0.97; P =.03).232 Parenteral selenium, the single antioxidant most likely to improve outcome,233,234 has shown a trend toward reducing mortality in patients with sepsis or septic shock (RR = 0.59; 95% CI 0.32-1.08; P = .08).232 Additional studies to delineate compatibility, optimal dosage, route, and optimal combination of antioxidants are needed. Renal function should be considered when supplementing vitamins and trace elements.

F3. The addition of enteral glutamine to an EN regimen (not already containing supplemental glutamine) should be considered in burn, trauma, and mixed ICU patients. (Grade: B)

Rationale. See Table 15 . 235-241 The addition of enteral glutamine to an EN regimen (non-glutamine supplemented) has been shown to reduce hospital and ICU length of stay in burn and mixed ICU patients,235,237 and mortality in burn patients alone237 compared to the same EN regimen without glutamine.

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 Level II Critically ill trauma (n = 80) EN/GLN 4/41 (10%) 20/35 (57%)a 32.7 ± 17.1 Hosp
EN 3/39 (8%) 26/37 (70%) 33.0 ± 23.8 Hosp
Jones et al,1999235 Level II Mixed ICU (n = 78) EN/GLN 10/26 (38%) NR 1 (4-54) ICU
EN 9/24 (38%) 16.5 (5-66) ICU
Brantley et al,2000239 Level II Critically ill trauma (n = 72) EN/GLN 0/31 (0%) NR 19.5 ± 8.8 Hosp
EN 0/41 (0%) 20.8 ± 11.5 Hosp
Hall et al,2003236 Level I Mixed ICU (n = 363) EN/GLN 27/179 (15%) 38/179 (21%) 25 (16-42) Hosp
EN 30/184 (16%) 43/184 (23%) 30 (19-45) Hosp
Garrel et al,2003237 Level II Burns (n = 45) Bloodstream
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 Level II Burns (n = 41) EN/GLN 0/20 (0%) 2/20 (10%)a 67 ± 4 Hosp
EN 0/20 (0%) 6/20 (30%) 73 ± 6 Hosp
Peng et al,2004241 Level II Burns (n = 48) EN/GLN NR NR 46.6 ± 12.9 Hosp
EN 55.7 ± 17.4 Hosp
  • SD, standard deviation; NR, not reported; ICU, intensive care unit; Hosp,hospital; LOS, length of stay. Adapted from the Canadian Clinical PracticeGuidelines.21
  • a P ≤ .05.

The glutamine powder, mixed with water to a consistency which allows infusion through the feeding tube, 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 not generate a sufficient systemic antioxidant effect, its favorable impact on outcome may be explained by its trophic influence on intestinal epithelium and maintenance of gut integrity. Enteral glutamine should not be added to an immune-modulating formulation already containing supplemental glutamine.237,238,240

F4. Soluble fiber may be beneficial for the fully resuscitated, hemodynamically stable critically ill patient receiving EN who develops diarrhea. Insoluble fiber should be avoided in all critically ill patients. Both soluble and insoluble fiber should be avoided in patients at high risk for bowel ischemia or severe dys-motility. (Grade: C)

Rationale. Three small level II studies using soluble partially hydrolyzed guar gum demonstrated a significant decrease in the incidence of diarrhea in patients receiving EN.242-244 However, no differences in days of mechanical ventilation, ICU, length of stay or multi-organ dysfunction syndrome (MODS) have been reported.242-244 Insoluble fiber has not been shown to decrease the incidence of diarrhea in the ICU patient. Cases of bowel obstruction in surgical and trauma patients who were provided enteral formulations containing insoluble fiber have been reported.245,246

G. When Indicated, Maximize Efficacy of Parenteral Nutrition

G1. If EN is not available or feasible, the need for PN therapy should be evaluated (see guidelines B1, B2, B3, C3). (Grade: C) If the patient is deemed to be a candidate for PN, steps to maximize efficacy (regarding dose, content, monitoring, and choice of supplemental additives) should be used. (Grade: C)

Rationale. As per the discussion for guidelines B1-3 and C3, a critically ill ICU patient may be an appropriate candidate for PN under certain circumstances:

  1. The patient is well nourished prior to admission, but after 7 days of hospitalization, EN has not been feasible or target goal calories have not been met consistently by EN alone.

  2. On admission, the patient is malnourished and EN is not feasible.

  3. A major surgical procedure is planned, the preoperative assessment indicates that EN is not feasible through the perioperative period, and the patient is malnourished.

For these patients, a number of steps may be used to maximize the benefit or efficacy of PN while reducing its inherent risk from hyperglycemia, immune suppression, increased oxidative stress, and potential infectious morbidity.24,92 The grade of the first recommendation is based on the strength of the literature for guidelines B1-3 and C3, while that of the second is based on the supportive data for guidelines G2-6.

G2. In all ICU patients receiving PN, mild permissive underfeeding should be considered at least initially. Once energy requirements are determined, 80% of these requirements should serve as the ultimate goal or dose of parenteral feeding. (Grade: C) Eventually, as the patient stabilizes, PN may be increased to meet energy requirements. (Grade: E) For obese patients (BMI30), the dose of PN with regard to protein and caloric provision should follow the same recommendations given for EN in guideline C5. (Grade: D)

Rationale. “Permissive underfeeding” in which the total caloric provision is determined by 80% of energy requirements (calculated from simplistic equations such as 25 kcal/kg actual body weight per day, published predictive equations, or as measured by indirect calorimetry) will optimize efficacy of PN. This strategy avoids the potential for insulin resistance, greater infectious morbidity, or prolonged duration of mechanical ventilation and increased hospital length of stay associated with excessive energy intake. In 2 studies, lower dose hypocaloric PN was shown to reduce the incidence of hyperglycemia247 and infections, ICU and hospital length of stay, and duration of mechanical ventilation compared to higher eucaloric doses of PN.248 See Table 16 . 247-250

Table 16. Randomized Studies Evaluating Lower Hypocaloric Doses (Hypocal) ofParenteral Nutrition (PN) vs Higher Eucaloric (Eucal) Doses of PN inCritically Ill Patients
Study Population Study Groups Mortality Infectionsa LOS Days, Mean ± SD (or Range) Ventilator Days, Mean ± SD (or range) Hyperglycemia
Battistella et al,1997248 Level II Trauma (n = 57) Pneumonia NR
Hypocal 2/27 (7%) ICU 13/27 (48%)b 18 ± 12ICUb 15 ± 12b
Eucal 0/30 (0%) ICU 22/30 (73%) 29 ± 22 ICU 27 ± 21
Bloodstream
Hypocal 5/27 (19%)b 27 ± 16Hospb
Eucal 13/30 (43%) 39 ± 24 Hosp
Choban et al,1997249 Level II ICU (n = 13) Hypocal 0/6 (0%) Hosp NR 48 ± 30 Hosp NR NR
Eucal 2/7 (29%) Hosp 45 ± 38 Hosp
McCowen et al,2000250 Level II ICU (n = 48) Hypocal 2/21 (10%) ICU 6/21 (29%) 19 ± 14 Hosp NR 4/21 (19%)
Eucal 3/19 (16%) ICU 10/19 (53%) 17 ± 15 Hosp 5/19 (26%)
Ahrens et al,2005247 Level II SICU (n = 40) Hypocal 1/20 (5%) ICU 5/20 (25%) 14 (10-21) ICU 10 (4-15) 5/20 (25%)b
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. Adapted from the Canadian Clinical PracticeGuidelines.21
  • a All infections represent number of patients per group with infection unlessotherwise stated.
  • b P ≤ .05.

G3. In the first week of hospitalization in the ICU, when PN is required and EN is not feasible, patients should be given a parenteral formulation without soy-based lipids. (Grade: D)

Rationale. This recommendation is controversial and is supported by a single level II study (which was also included in the hypocaloric vs eucaloric dosing in guideline G2 above).248 The recommendation is supported by animal data,251 with further support from EN studies,252 where long-chain fatty acids have been shown to be immunosuppressive. Currently in North America, the choice of parenteral lipid emulsion is severely limited to a soy-based 18-carbon ω-6 fatty acid preparation (which has proinflammatory characteristics in the ICU population). Over the first 7 days, soy-based lipid-free PN has been shown to be associated with a significant reduction in infectious morbidity (pneumonia and catheter-related sepsis), decreased hospital and ICU length of stay, and shorter duration of mechanical ventilation compared to use of lipid-containing PN.248 Combining the data from 2 studies,248,250 a meta-analysis by Heyland et al confirmed a significant reduction in infectious morbidity (RR = 0.63; 95% CI 0.42-0.93; P = .02) in the groups receiving no soy-based lipids.21 This recommendation should be applied with caution: these 2 studies were done prior to the Van den Berghe studies,253,254 and full dose PN without lipids might exacerbate stress-induced hyperglycemia. While 2 favorable level II studies would generate a grade C recommendation, the implications from a practical standpoint led to a downgrade of the recommendation to D. See Table 17 . 248,250

Table 17. Randomized Studies Evaluating Parenteral Nutrition (PN) With vs WithoutLipids in Critically Ill Patients
Study Population Study Groups ICU Mortality Infectionsa LOS Days, Mean ± SD Ventilator Days, Mean ± SD
Battistella et al,1997248 Level II Trauma (n = 57) Pneumonia
Without 2/27 (7%) 13/27 (48%)b 27 ± 16Hospb 15 ± 12b
With 0/30 (0%) 22/30 (73%) 39 ± 24 Hosp 27 ± 21
Line sepsis
5/27 (19%)b 18 ± 12ICUb
13/30 (43%) 29 ± 22 ICU
McCowen et al,2000250 Level II ICU (n = 48) Without 2/21 (10%) 6/21 (29%) 19 ± 14 Hosp NR
With 3/19 (16%) 10/19 (53%) 17 ± 15 Hosp
  • SD, standard deviation; NR, not reported; ICU, intensive care unit; LOS,length of stay. Adapted from the Canadian Clinical PracticeGuidelines.21
  • a All infections represent number of patients per group with infection unlessotherwise stated.
  • b P ≤ .05.

G4. A protocol should be in place to promote moderately strict control of serum glucose when providing nutrition support therapy. (Grade: B) A range of 110-150 mg/dL may be most appropriate. (Grade: E)

Rationale. Strict glucose control, keeping serum glucose levels between 80 and 110 mg/dL, has been shown in a large single center trial to be associated with reduced sepsis, reduced ICU length of stay, and lower hospital mortality when compared to conventional insulin therapy (keeping blood glucose levels <200 mg/dL).253 The effect was more pronounced in surgical ICU than medical ICU patients.254 See Table 18 . 253-255

Table 18. Randomized Studies Evaluating Intensive vs Moderate Control of Glucosein Critically Ill Patients
Study Population Study Groups Episodes of Hypoglycemia Clinical Outcomes Mortality
Van den Berghe et al,2001253 Level I Surgical ICU (n = 1548) Septicemia
Intensivecontrola 39/765 (51%)b 32/765 (4%) 35/765 (5%)ICUb
Conventionalcontrolc 6/783 (1%) 61/783 (8%) 63/783 (8%) ICU
Intensivecontrola 55/765 (7%)Hospb
Conventionalcontrolc 85/783 (11%) Hosp
Van den Berghe et al,2006254 Level I Medical ICU (n = 1200) New kidney injury All patients at day 3
Intensivecontrola 111/595 (19%)b 35/595 (6%)b 23/595 (3.9%) ICU
Conventionalcontrolc 19/605 (3%) 54/605 (9%) 17/605 (2.8%) ICU
Patients in ICU >3 d
Intensivecontrola 166/386 (43%)Hospb
Conventionalcontrolc 200/381 (52%) Hosp
Devos et al,2007255 Level I Mixed ICU (n = 1101) Intensivecontrola 9.8%b NR 17%
Moderatecontrold 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.

However, an as yet unpublished large level I multicenter European study suggested that moderate control (keeping glucose levels between 140 and 180 mg/dL) might avoid problems of hypoglycemia and subsequently reduce the mortality associated with hypoglycemia compared to tighter control.255 With a paucity of data, the Guidelines Committee felt that attempting to control glucose in the range of 110-150 mg/dL was most appropriate at this time.

G5. When PN is used in the critical care setting, consideration should be given to supplementation with parenteral glutamine. (Grade: C)

Rationale. The addition of parenteral glutamine (at a dose of 0.5 g/kg/d) to a PN regimen has been shown to reduce infectious complications,121,256 ICU length of stay,257 and mortality258 in critically ill patients, compared to the same PN regimen without glutamine. A meta-analysis by Heyland et al combining results from 9 studies confirmed a trend toward reduced infection (RR = 0.75; 96% CI 0.54-1.04; P = .08) and a significant reduction in mortality (RR = 0.67; 95% CI 0.48-0.92; P = .01) in groups receiving PN with parenteral glutamine versus those groups getting PN alone.21 See Table 19 . 121,256-264

Table 19. Randomized Studies Evaluating Parenteral Nutrition (PN) With vs WithoutSupplemental Parenteral Glutamine in Critically Ill Patients
Study Population Study Groups Mortality Infectionsa LOS Days, Mean ± SD (or Range)
Griffiths et al,1997259 &2002260 Level II ICU (n = 84) With 18/42 (43%) Hosp 28/42 (67%) 10.5 (6-19) ICU
Without 25/42 (60%) Hosp 26/42 (62%) 10.5 (6-24) ICU
Powell-Tuck et al,1999261 Level I ICU (n = 168) With 14/83 (17%) ICU NR 43.4 ± 34.1 Hosp
Without 20/85 (24%) ICU 48.9 ± 38.4 Hosp
Wischmeyer et al,2001262 Level II Burn (n = 31) With 2/15 (13%) ICU 7/12 (58%) 40 ± 10 Hosp
Without 5/16 (31%) ICU 9/14 (64%) 40 ± 9 Hosp
Goeters et al,2002258 Level II SICU (n = 68) With 7/33 (21%) ICU NR 21.3 ± 13.5 ICU
Without 10/35 (29%) ICU 20.8 ± 9.1 ICU
With 11/33 (33%) at 6mob 46 ± 49.1 Hosp
Without 21/35 (60%) at 6 mo 39.4 ± 31.1 Hosp
Fuentes-Orozco et al,2004256 Level II Peritonitis (n = 33) With 2/17 (12%) ICU 4/17 (24%)b 7.2 ± 9.2 ICU
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 Level II Postop surgery (n = 63) With 1/32 (3%) Hosp 8/30 (27%) 12 ± 2 ICUHospb
Without 5/31 (16%) Hosp 13/29 (45%) 23 ± 6 ICU Hosp
Zhou et al,2004263 Level II Burn (n = 30) With NR 3/15 (20%) 42 ± 7.0 Hosp
Without 4/15 (27%) 46 ± 6.6 Hosp
Xian-Li et al,2004121 Level II Acute pancreatitis (n = 69) With 0/20 (0%) ICU 0/20 (0%)b 25.3 ± 7.6 Hosp
Without 3/21 (14%) ICU 5/21 (24%) 28.6 ± 6.9 Hosp
Dechelotte et al,2006264 Level I ICU (n = 114) With 2/58 (3%) Hosp 23/58 (40%) 12.5 (1-430) ICU
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. Adapted from the Canadian Clinical PracticeGuidelines.21
  • a All infections represent number of patients per group with infection unlessotherwise stated.
  • b P ≤ .05.
  • c Pneumonia.

The proposed mechanism of this benefit relates to generation of a systemic antioxidant effect, maintenance of gut integrity, induction of heat shock proteins, and use as a fuel source for rapidly replicating cells. Of note, the dipeptide form of parenteral glutamine upon which most of these data are based is widely used in Europe but not commercially available in North America (referring both to the United States and Canada). Use of L-glutamine, the only source of parenteral glutamine available in North America, is severely limited by problems with stability and solubility (100 mL water per 2 g glutamine).256,264-267 All 3 reports which showed a positive clinical effect were level II studies,121,256,258 warranting a grade C recommendation.

G6. In patients stabilized on PN, periodically repeated efforts should be made to initiate EN. As tolerance improves and the volume of EN calories delivered increases, the amount of PN calories supplied should be reduced. PN should not be terminated until60% of target energy requirements are being delivered by the enteral route. (Grade: E)

Rationale. Because of the marked benefits of EN for the critically ill patient, repeated efforts to initiate enteral therapy should be made. To avoid the complications associated with overfeeding, the amount of calories delivered by the parenteral route should be reduced appropriately to compensate for the increase in the number of calories being delivered enterally. Once the provision of enteral feeding exceeds 60% of target energy requirements, PN may be terminated.

H. Pulmonary Failure

H1. Specialty high-lipid low-carbohydrate formulations designed to manipulate the respiratory quotient and reduce CO2 production are not recommended for routine use in ICU patients with acute respiratory failure. (Grade: E) (This is not to be confused with guideline E2 for ARDS/ALI).

Rationale. There is a lack of consensus about the optimum source and composition of lipids (medium- vs long-chain triglyceride, soybean oil, olive oil, ω-3 fatty acids, 10% or 20% solution) in enteral and parenteral formulations for the patient with respiratory failure. One small level II study (20 patients) showed a clinical benefit (reduced duration of mechanical ventilation) from use of a high-fat low-carbohydrate enteral formulation compared to a standard formulation.268 A second smaller level II study (10 patients) showed no clinical benefit.269 Results from uncontrolled studies suggest that increasing the composite ratio of fat to carbohydrate becomes clinically significant in lowering CO2 production only in the ICU patient being overfed and that composition is much less likely to affect CO2 production when the design of the nutrition support regimen approximates caloric requirements.270 Efforts should be made to avoid total caloric provision that exceeds energy requirements, as CO2 production increases significantly with lipogenesis and may be tolerated poorly in the patient prone to CO2 retention.268-270 Rapid infusion of fat emulsions (especially soybean-based), regardless of the total amount, should be avoided in patients suffering from severe pulmonary failure.

H2. Fluid-restricted calorically dense formulations should be considered for patients with acute respiratory failure. (Grade: E)

Rationale. Fluid accumulation and pulmonary edema are common in patients with acute respiratory failure and have been associated with poor clinical outcomes. It is therefore suggested that a fluid-restricted calorically dense nutrient formulation (1.5-2.0 kcal/mL) be considered for patients with acute respiratory failure that necessitates volume restriction.269

H3. Serum phosphate levels should be monitored closely and replaced appropriately when needed. (Grade: E)

Rationale. Phosphate is essential for the synthesis of adenosine triphosphate (ATP) and 2,3-disphosphoglycerate (2,3-DPG), both of which are critical for normal diaphragmatic contractility and optimal pulmonary function. Length of stay and duration of mechanical ventilation are increased in patients who become hypophosphatemic when compared to those who do not have this electrolyte imbalance. As suggested by several uncontrolled studies, it therefore seems prudent to monitor phosphate closely and replace appropriately when needed.271,272

I. Renal Failure

I1. ICU patients with acute renal failure (ARF) or acute kidney injury (AKI) should be placed on standard enteral formulations, and standard ICU recommendations for protein and calorie provision should be followed. If significant electrolyte abnormalities exist or develop, a specialty formulation designed for renal failure (with appropriate electrolyte profile) may be considered. (Grade: E)

Rationale. ARF seldom exists as an isolated organ failure in critically ill patients. When prescribing EN to the ICU patient, the underlying disease process, preexisting comorbidities, and current complications should be taken into account. Specialty formulations lower in certain electrolytes (ie, phosphate and potassium) than standard products may be beneficial in the ICU patient with ARF.273-275

I2. Patients receiving hemodialysis or continuous renal replacement therapy (CRRT) should receive increased protein, up to a maximum of 2.5 g/kg/d. Protein should not be restricted in patients with renal insufficiency as a means to avoid or delay initiation of dialysis therapy. (Grade: C)

Rationale. There is an approximate amino acid loss of 10-15 g/d during CRRT. Providing <1 g/kg/d of protein may result in increased nitrogen deficits for patients on hemodialysis or CRRT. Patients undergoing CRRT should receive formulations with 1.5-2.0 g/kg/d of protein. At least 1 randomized prospective trial276 has suggested an intake of 2.5 g/kg/d is necessary to achieve positive nitrogen balance in this patient population.276-278

J. Hepatic Failure

J1. Traditional assessment tools should be used with caution in patients with cirrhosis and hepatic failure, as these tools are less accurate and less reliable due to complications of ascites, intravascular volume depletion, edema, portal hypertension, and hypoalbuminemia. (Grade: E)

Rationale. While malnutrition is highly prevalent among patients with chronic liver disease and nearly universal among patients awaiting liver transplantation, the clinical consequences of liver failure render traditional nutrition assessment tools inaccurate and unreliable. The primary etiology of malnutrition is poor oral intake stemming from multiple factors. Malnutrition in patients with cirrhosis leads to increased morbidity and mortality rates. Furthermore, patients who are severely malnourished before transplant surgery have a higher rate of complications and a decreased overall survival rate after liver transplantation. Energy needs in critically ill patients with liver disease are highly variable, are difficult to predict by simple equations in liver disease, and consequently are best determined by indirect calorimetry in ICU patients with liver disease.279-287

J2. EN is the preferred route of nutrition therapy in ICU patients with acute and/or chronic liver disease. Nutrition regimens should avoid restricting protein in patients with liver failure. (Grade: E)

Rationale. Nutrition therapy is essential in patients with end-stage liver disease and during all phases of liver transplantation. EN has been associated with decreased infection rates and fewer metabolic complications in liver disease and after liver transplant when compared to PN. Long-term PN can be associated with hepatic complications, including worsening of existing cirrhosis and liver failure with the concomitant risks of sepsis, coagulopathy, and death. Nutrition-associated cholestasis usually present with prolonged PN is also a significant problem. EN improves nutrition status, reduces complications, and prolongs survival in liver disease patients and is therefore recommended as the optimal route of nutrient delivery. Protein should not be restricted as a management strategy to reduce risk of developing hepatic encephalopathy.279,282 Protein requirements for the patient with hepatic failure should be determined in the same manner as for the general ICU patient (in keeping with guidelines C4 and C5).

J3. Standard enteral formulations should be used in ICU patients with acute and chronic liver disease. Branched chain amino acid formulations (BCAA) should be reserved for the rare encephalopathic patient who is refractory to standard treatment with luminal acting antibiotics and lactulose. (Grade: C)

Rationale. There is no evidence to suggest that a formulation enriched in BCAA improves patient outcomes compared to standard whole protein formulations in critically ill patients with liver disease. Findings from level II randomized outpatient trials suggest that long-term (12 and 24 months) nutritional supplementation with oral BCAA granules may be useful in slowing the progression of hepatic disease and/or failure and prolonging event-free survival. In patients with hepatic encephalopathy refractory to usual therapy, use of BCAA formulations may improve coma grade compared to standard formulations.279,288-292

K. Acute Pancreatitis

K1. On admission, patients with acute pancreatitis should be evaluated for disease severity. (Grade: E) Patients with severe acute pancreatitis should have a nasoenteric tube placed and EN initiated as soon as fluid volume resuscitation is complete. (Grade: C)

Rationale. Based on the Atlanta Classification,293 patients with severe acute pancreatitis may be identified on admission by the presence of organ failure and/or the presence of local complications within the pancreas on computerized tomography (CT) scan, complemented by the presence of unfavorable prognostic signs.293,294 Organ failure is defined by shock (systolic blood pressure <90 mm Hg), pulmonary insufficiency (Pao2 <60 mm Hg), renal failure (serum creatinine >2 mg/dL), or GI bleeding (>500 mL blood loss within 24 hours). Local complications on CT scan include pseudocyst, abscess, or necrosis. Unfavorable prognostic signs are defined by an Acute Physiology and Chronic Health Evaluation (APACHE) II score of ≥8 or by ≥3 Ranson Criteria.293,294 Patients with severe acute pancreatitis have an increased rate of complications (38%) and a higher mortality (19%) than patients with mild to moderate disease and have close to 0% chance of advancing to oral diet within 7 days.97,295,296 Loss of gut integrity with increased intestinal permeability is worse with greater disease severity.9

Patients with severe acute pancreatitis will experience improved outcome when provided early EN. Three meta-analyses of varying combinations of ten level II randomized trials8,22,46,54-60 showed that use of EN compared to PN reduces infectious morbidity (RR = 0.46; 95% CI 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 surgical intervention (RR = 0.48; 95% CI 0.23-0.99; P = .05),297 multiple organ failure (OR = 0.306; 95% CI 0.128-0.736; P = .008),298 and mortality (OR = 0.251; 95% CI 0.095-0.666; P = .005).298 See Table 3 . 8,22,46,54-60 In a meta-analysis of 2 studies18,19 in patients operated on for complications of severe acute pancreatitis, there was a trend toward reduced mortality with use of early EN started the day after surgery (RR = 0.26; 95% CI 0.06-1.09; P =.06) compared to STD therapy where no nutrition support therapy was provided.17

The need to initiate EN early within 24-48 hours of admission is supported by the fact that out of six level II studies done only in patients with severe acute pancreatitis, 5 studies which randomized and initiated EN within 48 hours of admission all showed significant outcome benefits22,56,58-60 compared to PN. Only 1 study in severe pancreatitis which randomized patients and started EN after 4 days showed no significant outcome benefit.57

K2. Patients with mild to moderate acute pancreatitis do not require nutrition support therapy (unless an unexpected complication develops or there is failure to advance to oral diet within 7 days). (Grade: C)

Rationale. Patients with mild to moderate acute pancreatitis have a much lower rate of complications (6%) than patients with more severe disease, have close to a 0% mortality rate, and have an 81% chance of advancing to oral diet within 7 days.97,295,296 Providing nutrition support therapy to these patients does not appear to change outcome. Out of three level II randomized studies which included patients with less disease severity (62%-81% of patients had mild to moderate acute pancreatitis), none showed significant outcome benefits with use of EN compared to PN.8,46,55 Provision of nutrition support therapy in these patients should be considered if a subsequent unanticipated complication develops (eg, sepsis, shock, organ failure) or the patient fails to advance to oral diet after 7 days of hospitalization.

K3. Patients with severe acute pancreatitis may be fed enterally by the gastric or jejunal route. (Grade: C)

Rationale. Two level II prospective randomized trials comparing gastric with jejunal feeding in patients with severe acute pancreatitis showed no significant differences between the 2 levels of EN infusion within the GI tract.299,300 The success of gastric feeding in these 2 studies (where only 2 patients in the Eatock et al group299 and 1 patient in the Kumar et al group300 experienced increased pain only without a need to reduce the infusion rate) was attributed to early initiation of feeding within 36-48 hours of admission, thereby minimizing the degree of ileus.299

K4. Tolerance to EN in patients with severe acute pancreatitis may be enhanced by the following measures:

  • Minimizing the period of ileus after admission by early initiation of EN. (Grade: D)

  • Displacing the level of infusion of EN more distally in the GI tract. (Grade: C)

  • Changing the content of the EN delivered from intact protein to small peptides, and long-chain fatty acids to medium-chain triglycerides or a nearly fat-free elemental formulation. (Grade: E)

  • Switching from bolus to continuous infusion. (Grade: C)

Rationale. In a prospective level III study, Cravo et al showed that the longer the period of ileus and the greater the delay in initiating EN, the worse the tolerance (and the greater the need to switch to PN) in patients admitted with severe acute pancreatitis. Delays of ≥6 days resulted in 0% tolerance of EN, whereas initiating EN within 48 hours was associated with 92% tolerance.301

Feeding higher in the GI tract is more likely to stimulate pancreatic exocrine secretion, which may invoke greater difficulties with tolerance. Conversely, feeding into the jejunum 40 cm or more below the ligament of Treitz is associated with little or no pancreatic exocrine stimulation.302 In a level II prospective trial, McClave et al showed varying degrees of tolerance with different levels of infusion within the GI tract.46 Three patients who tolerated deep jejunal feeding with an EN formulation developed an uncomplicated exacerbation of symptoms with advancement to oral clear liquids (an effect which was reversed by return to jejunal feeding). One patient who showed tolerance to jejunal feeds had an exacerbation of the systemic inflammatory response syndrome (SIRS) when the tube was displaced back into the stomach (an effect which again was reversed by return to jejunal feeding).46

At the same level of infusion within the GI tract, content of EN formulation may be a factor in tolerance. In a prospective case series, patients hospitalized for acute pancreatitis who could not tolerate a regular diet showed resolution of symptoms and normalization of amylase levels after switching to an oral, nearly fat-free elemental EN formulation.303 In a patient operated on for complications of severe acute pancreatitis, feeding a nearly fat-free elemental EN formulation had significantly less pancreatic exocrine stimulation (measured by lipase output from the ampulla) than a standard EN formulation with intact long-chain fatty acids infused at the same level of the jejunum.304

The manner of infusion of EN also affects tolerance. A small level II randomized trial showed that continuous infusion of EN into the jejunum (100 mL over 60 minutes) was associated with significantly less volume, bicarbonate, and enzyme output from the pancreas than the same volume given as an immediate bolus.305 It is not clear whether the data from this study can be extrapolated to gastric feeding. (Note: The Guidelines Committee does not recommend bolus feeding into the jejunum.)

K5. For the patient with severe acute pancreatitis, when EN is not feasible, use of PN should be considered. (Grade: C) PN should not be initiated until after the first 5 days of hospitalization. (Grade: E)

Rationale. For patients with severe acute pancreatitis, when EN is not feasible, timing of initiation of PN (and the choice between PN and STD therapy) becomes an important issue. In an early level II randomized trial, Sax et al showed net harm from use of PN initiated within 24 hours of admission for patients with mild to moderate acute pancreatitis, with significantly longer hospital length of stay than those patients randomized to STD therapy (no nutrition support therapy).97 In contrast, in a later level II study by Xian-Li et al in patients with severe pancreatitis whereby PN was initiated 24-48 hours after “full liquid resuscitation,” significant reductions in overall complications, hospital length of stay, and mortality were seen when compared to STD therapy.121 The design of this latter study may have led to a differential delay of several days in the initiation of PN, possibly after the peak of the inflammatory response.17 The grade of the first recommendation (to consider use of PN) is based on the results of the level II study by Xian-Li et al,121 whereas the grade for the second recommendation (regarding the timing of PN) is based on expert opinion and interpretation of the discrepancy between these 2 reports.97,121

L. Nutrition Therapy in End-of-Life Situations

L1. Specialized nutrition therapy is not obligatory in cases of futile care or end-of-life situations. The decision to provide nutrition therapy should be based on effective patient/family communication, realistic goals, and respect for patient autonomy. (Grade: E)

Rationale. Healthcare providers are not obligated to initiate nutrition support therapy in end-of-life situations. Dehydration and starvation are well tolerated and generate little symptomatology in the vast majority of patients. In this unfortunate setting, provision of EN or PN therapy has not been shown to improve outcome. Nonetheless, cultural, ethnic, religious, or individual patient issues may in some circumstances necessitate delivery of nutrition support therapy.306,307

  • These guidelines are also being co-published by the Society of Critical Care Medicine (SCCM) in Critical Care Medicine, 2009; volume 37, number 5.
  • Authors' Disclosures—Potential Conflicts of Interest
  • Speaker's bureaus, consultant fees, or research grants: Stephen A. McClave, MD (Nestle, Abbott, ACM Technologies, Kimberly-Clark, Microvasive Boston Scientific); Robert G. Martindale, MD (Nestle, Abbott, Merck); Beth Taylor, RD (Nestle); Pamela Roberts, MD (Nestle and Abbott); and Juan Ochoa, MD (Nestle and Abbott).
  • Direct financial intereststock ($10,000 or more): none.
  • Authors with no relationship to disclose: Vincent W. Vanek, MD; Gail Cresci, RD; Mary McCarthy, RN, PhD; and Lena M. Napolitano, MD.
  • A.S.P.E.N. Board of Directors Providing Final Approval
  • Kelly A. Tappenden, RD, PhD; Vincent W. Vanek, MD; Stephen A. McClave, MD; Jay M. Mirtallo, RPh, BSNSP; Ainsley M. Malone, RD, MS; Lawrence A. Robinson, PharmD; Charles Van Way III, MD; Elizabeth M. Lyman, RN, MSN; John R. Wesley, MD; Mark R. Corkins, MD; and Tom Jaksic, MD, PhD.
  • SCCM Council Providing Final Approval
  • Philip S. Barie, MD, MBA; Mitchell M. Levy, MD; Judith Jacobi, PharmD; Pamela A. Lipsett, MD; Frederick P. Ognibene, MD; Alice D. Ackerman, MD; Thomas P. Bleck, MD; Richard J. Brilli, MD; Craig M. Coopersmith, MD; Joseph F. Dasta, MSc; Clifford S. Deutschman, MD; Todd Dorman, MD; J. Christopher Farmer, MD; Heidi L. Frankel, MD; Steven J. Martin, PharmD; Barbara McLean, MN, CCRN, CCNS-NP; Carol Thompson, PhD, CCRN; and Janice L. Zimmerman, MD.
  • American College of Critical Care Medicine Board of Regents Providing Final Approval
  • Antoinette Spevetz, MD; Timothy S. Yeh, MD; M. Michele Moss, MD; Lena M. Napolitano, MD; E. Daleen Aragon, RN, PhD, CCRN; Sandralee A. Blosser, MD; Richard D. Branson, MS, RRT; Gerard J. Fulda, MD; Edgar Jimenez, MD; and Michael J. Murray, MD, PhD.
  • Acknowledgments

    The Canadian Clinical Practice Guidelines (CPGs)21 served as an indispensable reference source and a valuable model for the organization of the topics included in this document. Many of the tables were adapted from the CPGs.