This Article Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by McClave, S. A. Search for Related Content PubMed PubMed Citation Articles by McClave, S. A. Social Bookmarking                         What's this?

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.)

Address correspondence to: Steven A. McClave, MD, Division of Gastroenterology/Hepatology, University of Louisville, 550 South Jackson Street, Louisville, KY 40292; email: samcclave{at}louisville.edu.

	Preliminary Remarks

Top Preliminary Remarks Introduction

 
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

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

Top Preliminary Remarks 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

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}

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

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}

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 studies^93-99 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 studies^{96,97,100,101} 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

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 nutri tion 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 be 7 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 seven^{95,98,102,103,107,110,111} out of 14 studies^{94,100,104,106,108,109,112} 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 PN^{93,94,96,99-101,104,109,122} 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 cost^137,138 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

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 range 2.0 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 (BMI 40). 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}

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

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

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

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, -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 -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 -3 fatty acids eicosapentaenoic acid (EPA) and docosohexaenoic acid (DHA) displace -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 (NFB), 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.

Multiple meta-analyses^{181,182,210-212} 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

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 better^195,197 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, -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 -3 fatty acids (in the form of EPA), borage oil (-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

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.

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 (BMI 30), 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

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 -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

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

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

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 until 60% 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, -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 trials^{8,22,46,54-60} 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 studies^18,19 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 benefits^22,56,58-60 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

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.

Top Preliminary Remarks Introduction

 
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 interest—stock ($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.

1. Dellinger RP, Carlet JM, Masur H, et al; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med.2004; 32:858 -873.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
2. Martindale RG, Maerz LL. Management of perioperative nutrition support. Curr Opin Crit Care.2006; 12:290 -294.[Web of Science][Medline] [Order article via Infotrieve]
3. Raguso CA, Dupertuis YM, Pichard C. The role of visceral proteins in the nutritional assessment of intensive care unit patients. Curr Opin Clin Nutr Metab Care. 2003;6:211 -216.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
4. Kudsk KA. Current aspects of mucosal immunology and its influence by nutrition. Am J Surg.2002; 183:390 -398.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
5. Jabbar A, Chang WK, Dryden GW, McClave SA. Gut immunology and the differential response to feeding and starvation. Nutr Clin Pract. 2003;18:461 -482.[Abstract/Free Full Text]
6. Kang W, Kudsk KA. Is there evidence that the gut contributes to mucosal immunity in humans? JPEN J Parenter Enteral Nutr.2007; 31:246 -258.[Abstract/Free Full Text]
7. Kang W, Gomez FE, Lan J, Sano Y, Ueno C, Kudsk KA. Parenteral nutrition impairs gut-associated lymphoid tissue and mucosal immunity by reducing lymphotoxin beta receptor expression. Ann Surg.2006; 244:392 -399.[Web of Science][Medline] [Order article via Infotrieve]
8. Windsor AC, Kanwar S, Li AG, et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut.1998; 42:431 -435.[Abstract/Free Full Text]
9. Ammori BJ, Leeder PC, King RF, et al. Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality. J Gastrointest Surg.1999; 3:252 -262.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
10. Lewis SJ, Egger M, Sylvester PA, et al. Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled studies. Br Med J.2001; 323:1 -5.[Free Full Text]
11. Schroeder D, Gillanders L, Mahr K, Hill GL. Effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing. JPEN J Parenter Enteral Nutr.1991; 15:376 -383.[Abstract/Free Full Text]
12. Sagar S, Harland P, Shields R. Early postoperative feeding with elemental diet. Br Med J.1979; 1:293 -295.[Abstract/Free Full Text]
13. Carr CS, Ling KD, Boulos P, Singer M. Randomised trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection. BMJ.1996; 12:869 -871.
14. Beier-Holgersen R, Boesby S. Influence of postoperative enteral nutrition on postsurgical infections. Gut.1996; 39:833 -835.[Abstract/Free Full Text]
15. Heslin MJ, Latkany L, Leung D, et al. A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg.1997; 226:567 -577.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
16. Watters JM, Kirkpatrick SM, Norris SB, Shamji FM, Wells GA. Immediate postoperative enteral feeding results in impaired respiratory mechanics and decreased mobility. Ann Surg.1997; 226:369 -377.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
17. McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. JPEN J Parenter Enteral Nutr. 2006;30:143 -156.[Abstract/Free Full Text]
18. Pupelis G, Austrums E, Jansone A, Sprucs R, Wehbi H. Randomised trial of safety and efficacy of postoperative enteral feeding in patients with severe pancreatitis: preliminary report. Eur J Surg.2000; 166:383 -387.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
19. Pupelis G, Selga G, Austrums E, Kaminski A. Jejunal feeding, even when instituted late, improves outcomes in patients with severe pancreatitis and peritonitis. Nutrition.2001; 17:91 -94.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
20. Kudsk KA, Croce MA, Fabian TC, et al. Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg. 1992;215:503 -513.[Web of Science][Medline] [Order article via Infotrieve]
21. Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P; Canadian Critical Care Clinical Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr.2003; 27:355 -373.[Abstract/Free Full Text]
22. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg.1997; 84:1665 -1669.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
23. Taylor SJ, Fettes SB, Jewkes C, Nelson RJ. Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury.Crit Care Med. 1999;27:2525 -2531.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
24. Braunschweig CL, Levy P, Sheean PM, Wang X. Enteral compared with parenteral nutrition: a meta-analysis. Am J Clin Nutr.2001; 74:534 -542.[Abstract/Free Full Text]
25. Simpson F, Doig GS. Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med.2005; 31:12 -23.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
26. Gramlich L, Kichian K, Pinilla J, Rodych NJ, Dhaliwal R, Heyland DK. Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature. Nutrition.2004; 20:843 -848.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
27. Moore FA, Feliciano DV, Andrassy RJ, et al. Early enteral feeding, compared with parenteral, reduces postoperative septic complications: the results of a meta-analysis. Ann Surg.1992; 216:172 -183.[Web of Science][Medline] [Order article via Infotrieve]
28. Peter JV, Moran JL, Phillips-Hughes J. A metaanalysis of treatment outcomes of early enteral versus early parenteral nutrition in hospitalized patients. Crit Care Med.2005; 33:213 -220.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
29. Rapp RP, Young DB, Twyman D. The favorable effect of early parenteral feeding on survival in head-injured patients. J Neurosurg. 1983;58:906 -912.[Web of Science][Medline] [Order article via Infotrieve]
30. Adams S, Dellinger EP, Wertz MJ. Enteral versus parenteral nutritional support following laparotomy for trauma: a randomized prospective trial. J Trauma. 1986;26:882 -891.[Web of Science][Medline] [Order article via Infotrieve]
31. Bower RH, Talamini MA, Sax HC. Postoperative enteral vs parenteral nutrition: a randomized controlled trial. Arch Surg.1986; 121:1040 -1045.[Abstract/Free Full Text]
32. Szeluga DJ, Stuart RK, Brookmeyer R, Utermohlen V, Santos GW. Nutritional support of bone marrow transplant recipients: a prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program. Cancer Res.1987; 47:3309 -3316.[Abstract/Free Full Text]
33. Young B, Ott L, Haack D. Effect of total parenteral nutrition upon intracranial pressure in severe head injury. J Neurosurg.1987; 67:76 -80.[Web of Science][Medline] [Order article via Infotrieve]
34. Peterson VM, Moore EE, Jones TN, et al. Total enteral nutrition versus total parenteral nutrition after major torso injury: attenuation of hepatic protein reprioritization. Surgery.1988; 104:199 -207.[Web of Science][Medline] [Order article via Infotrieve]
35. Cerra FB, McPherson JP, Konstantinides FN, Konstantinides NN, Teasley KM. Enteral nutrition does not prevent multiple organ failure syndrome (MOFS) after sepsis. Surgery.1988; 104:727 -733.[Web of Science][Medline] [Order article via Infotrieve]
36. Greenberg GR, Fleming CR, Jeejeebhoy KN, Rosenberg IH, Sales D, Tremaine WJ. Controlled trial of bowel rest and nutritional support in the management of Crohn's disease. Gut.1988; 29:1309 -1315.[Abstract/Free Full Text]
37. Moore FA, Moore EE, Jones TN, McCroskey BL, Peterson VM. TEN versus TPN following major abdominal trauma: reduced septic morbidity. J Trauma. 1989;29:916 -923.[Web of Science][Medline] [Order article via Infotrieve]
38. Hamaoui E, Lefkowitz R, Olender L, et al. Enteral nutrition in the early postoperative period: a new semi-elemental formula versus total parenteral nutrition. JPEN J Parenter Enteral Nutr.1990; 14:501 -507.[Abstract/Free Full Text]
39. González-Huix F, Fernández-Bañares F, Esteve-Comas M, et al. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis. Am J Gastroenterol.1993; 88:227 -232.[Web of Science][Medline] [Order article via Infotrieve]
40. Iovinelli G, Marsili I, Varrassi G. Nutrition support after total laryngectomy. JPEN J Parenter Enteral Nutr.1993; 17:445 -448.[Abstract/Free Full Text]
41. Kudsk KA, Minard G, Wojtysiak SL, Croce M, Fabian T, Brown RO. Visceral protein response to enteral versus parenteral nutrition and sepsis in patients with trauma. Surgery.1994; 116:516 -523.[Web of Science][Medline] [Order article via Infotrieve]
42. Dunham CM, Frankenfield D, Belzberg H, Wiles C, Cushing B, Grant Z. Gut failure-predictor of or contributor to mortality in mechanically ventilated blunt trauma patients? J Trauma1994; 37:30 -34.[Web of Science][Medline] [Order article via Infotrieve]
43. Borzotta AP, Pennings J, Papasadero B, et al. Enteral versus parenteral nutrition after severe closed head injury. J Trauma1994; 37:459 -468.[Web of Science][Medline] [Order article via Infotrieve]
44. Hadfield RJ, Sinclair DG, Houldsworth PE, Evans TW. Effects of enteral and parenteral nutrition on gut mucosal permeability in the critically ill. Am J Respir Crit Care Med.1995; 152:1545 -1548.[Abstract]
45. Baigrie RJ, Devitt PG, Watkin DS. Enteral versus parenteral nutrition after oesophagogastric surgery: a prospective randomized comparison.Aust N Z J Surg. 1996;66:668 -670.[Web of Science][Medline] [Order article via Infotrieve]
46. McClave SA, Greene LM, Snider HL, et al. Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis.JPEN J Parenter Enteral Nutr.1997; 21:14 -20.[Abstract/Free Full Text]
47. Reynolds JV, Kanwar S, Welsh FK, et al. Does the route of feeding modify gut barrier function and clinical outcome in patients after major upper gastrointestinal surgery? JPEN J Parenter Enteral Nutr.1997; 21:196 -201.[Abstract/Free Full Text]
48. Sand J, Luostarinen M, Matikainen M. Enteral or parenteral feeding after total gastrectomy: prospective randomised pilot study. Eur J Surg. 1997;163:761 -766.[Web of Science][Medline] [Order article via Infotrieve]
49. Gianotti L, Braga M, Vignali A, et al. Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch Surg.1997; 132:1222 -1230.[Abstract/Free Full Text]
50. Woodcock NP, Zeigler D, Palmer MD, Buckley P, Mitchell CJ, Macfie J. Enteral versus parenteral nutrition: a pragmatic study.Nutrition. 2001;17:1 -12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
51. Braga M, Gianotti L, Gentilini O, Parisi V, Salis C, Di C. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med.2001; 29:242 -248.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
52. Pacelli F, Bossola M, Papa V, et al. Enteral vs parenteral nutrition after major abdominal surgery: an even match. Arch Surg. 2001;136:933 -936.[Abstract/Free Full Text]
53. Bozzetti F, Braga M, Gianotti L, Gavazzi C, Mariani L. Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: a randomised multicentre trial.Lancet. 2001;358:1487 -1492.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
54. Oláh A, Pardavi G, Belágyi T, Nagy A, Issekutz A, Mohamed GE. Early nasojejunal feeding in acute pancreatitis is associated with a lower complication rate. Nutrition.2002; 18:259 -262.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
55. Abou-Assi S, Craig K, O'Keefe SJ. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol.2002; 97:2255 -2262.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
56. Gupta R, Patel K, Calder PC, Yaqoob P, Primrose JN, Johnson CD. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II 6). Pancreatology. 2003;3:406 -413.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
57. Louie BE, Noseworthy T, Hailey D, Gramlich LM, Jacobs P, Warnock GL. Enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. Can J Surg.2005; 48:298 -306.[Web of Science][Medline] [Order article via Infotrieve]
58. Petrov MS, Kukosh MV, Emelyanov NV. A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition. Dig Surg. 2006;23:336 -344.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
59. Eckerwall GE, Axelsson JB, Andersson RG. Early nasogastric feeding in predicted severe acute pancreatitis: a clinical, randomized study.Ann Surg. 2006;244:959 -967.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
60. Casas M, Mora J, Fort E, et al. Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis. Rev Esp Enferm Dig. 2007;99:264 -269.[Web of Science][Medline] [Order article via Infotrieve]
61. Shirabe K, Matsumata T, Shimada M, et al. A comparison of parenteral hyperalimentation and early enteral feeding regarding systemic immunity after major hepatic resection: the results of a randomized prospective study. Hepatogastroenterology.1997; 44:205 -209.[Medline] [Order article via Infotrieve]
62. Marik PE, Zaloga GP. Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med.2001; 29:2264 -2270.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
63. Moore EE, Jones TN. Benefits of immediate jejunostomy feeding after major abdominal trauma: a prospective, randomized study. J Trauma. 1986;26:874 -881.[Web of Science][Medline] [Order article via Infotrieve]
64. Chiarelli A, Enzi G, Casadei A, Baggio B, Valerio A, Mazzoleni F. Very early nutrition supplementation in burned patients. Am J Clin Nutr. 1990;51:1035 -1039.[Abstract/Free Full Text]
65. Eyer SD, Micon LT, Konstantinides FN, et al. Early enteral feeding does not attenuate metabolic response after blunt trauma. J Trauma. 1993;34:639 -643.[Web of Science][Medline] [Order article via Infotrieve]
66. Chuntrasakul C, Siltharm S, Chinswangwatanakul V, Pongprasobchai T, Chockvivatanavanit S, Bunnak A. Early nutritional support in severe traumatic patients. J Med Assoc Thai.1996; 79:21 -26.[Medline] [Order article via Infotrieve]
67. Singh G, Ram RP, Khanna SK. Early post-operative enteral feeding in patients with nontraumatic intestinal perforation and peritonitis. J Am Coll Surg. 1998;187:142 -146.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
68. Minard G, Kudsk KA, Melton S, Patton JH, Tolley EA. Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries. JPEN J Parenter Enteral Nutr.2000; 24:145 -149.[Abstract/Free Full Text]
69. Kompan L, Vidmar G, Spindler-Vesel A, Pecar J. Is early enteral nutrition a risk factor for gastric intolerance and pneumonia? Clin Nutr. 2004;23:527 -532.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
70. Malhotra A, Mathur AK, Gupta S. Early enteral nutrition after surgical treatment of gut perforations: a prospective randomised study.J Postgrad Med. 2004;50:102 -106.[Medline] [Order article via Infotrieve]
71. Peck MD, Kessler M, Cairns BA, Chang YH, Ivanova A, Schooler W. Early enteral nutrition does not decrease hypermetabolism associated with burn injury. J Trauma. 2004;57:1143 -1149.[Web of Science][Medline] [Order article via Infotrieve]
72. Dvorak MF, Noonan VK, Belanger L, et al. Early versus late enteral feeding in patients with acute cervical spinal cord injury: a pilot study.Spine. 2004;29:E175 -E180.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
73. McClave SA, Chang WK. Feeding the hypotensive patient: does enteral feeding precipitate or protect against ischemic bowel? Nutr Clin Pract. 2003;18:279 -284.[Abstract/Free Full Text]
74. Melis M, Fichera A, Ferguson MK. Bowel necrosis associated with early jejunal tube feeding: a complication of postoperative enteral nutrition.Arch Surg. 2006;141:701 -704.[Abstract/Free Full Text]
75. Zaloga GP, Roberts PR, Marik P. Feeding the hemodynamically unstable patient: a critical evaluation of the evidence. Nutr Clin Pract. 2003;18:285 -293.[Free Full Text]
76. Kozar RA, McQuiggan MM, Moore EE, Kudsk KA, Jurkovich GJ, Moore FA. Postinjury enteral tolerance is reliably achieved by a standardized protocol.J Surg Res. 2002;104:70 -75.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
77. Mutlu GM, Mutlu EA, Factor P. Prevention and treatment of gastrointestinal complications in patients on mechanical ventilation.Am J Respir Med. 2003;2:395 -411.[Medline] [Order article via Infotrieve]
78. Lien HC, Chang CS, Chen GH. Can percutaneous endoscopic jejunostomy prevent gastroesophageal reflux in patients with preexisting esophagitis?Am J Gastroenterol.2000; 95:3439 -3443.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
79. Heyland DK, Drover JW, MacDonald S, Novak F, Lam M. Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration: results of a randomized controlled trial. Crit Care Med. 2001;29:1495 -1501.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
80. Ho KM, Dobb GJ, Webb SA. A comparison of early gastric and post-pyloric feeding in critically ill patients: a meta-analysis.Intensive Care Med.2006; 32:639 -649.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
81. Marik PE, Zaloga GP. Gastric versus post-pyloric feeding: a systematic review. Crit Care.2003; 7:R46 -R51.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
82. Heyland DK, Drover JW, Dhaliwal R, Greenwood J. Optimizing the benefits and minimizing the risks of enteral nutrition in the critically ill: role of small bowel feeding. JPEN J Parenter Enteral Nutr.2002; 26(6 suppl):S51 -S55.[Abstract/Free Full Text]
83. Montecalvo MA, Steger KA, Farber HW, et al. Nutritional outcome and pneumonia in critical care patients randomized to gastric versus jejunal tube feedings. The Critical Care Research Team. Crit Care Med.1992; 20:1377 -1387.[Web of Science][Medline] [Order article via Infotrieve]
84. Kortbeek JB, Haigh PI, Doig C. Duodenal versus gastric feeding in ventilated blunt trauma patients: a randomized controlled trial. J Trauma. 1999;46:992 -996.[Web of Science][Medline] [Order article via Infotrieve]
85. Kearns LJ, Chin D, Mueller L, Wallace K, Jensen WA, Kirsch CM. The incidence of ventilator-associated pneumonia and success in nutrient delivery with gastric versus small intestinal feeding: a randomized clinical trial.Crit Care Med. 2000;28:1742 -1746.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
86. Day HE, Badiani A, Uslaner JM, et al. Environmental novelty differentially affects c-fos mRNA expression induced by amphetamine or cocaine in subregions of the bed nucleus of the stria terminalis and amygdala.J Neurosci. 2001;21:732 -740.[Abstract/Free Full Text]
87. Esparza J, Boivin MA, Hartshorne MF, Levy H. Equal aspiration rates in gastrically and transpylorically fed critically ill patients.Intensive Care Med.2001; 27:660 -664.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
88. Boivin MA, Levy H. Gastric feeding with erythromycin is equivalent to transpyloric feeding in the critically ill. Crit Care Med.2001; 29:1916 -1919.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
89. Neumann DA, DeLegge MH. Gastric versus small-bowel tube feeding in the intensive care unit: a prospective comparison of efficacy. Crit Care Med. 2002;30:1436 -1438.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
90. Davies AR, Froomes PR, French CJ, et al. Randomized comparison of nasojejunal and nasogastric feeding in critically ill patients. Crit Care Med. 2002;30:586 -590.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
91. Montejo JC, Grau T, Acosta J, et al. Multicenter, prospective, randomized, single-blind study comparing the efficacy and gastrointestinal complications of early jejunal feeding with early gastric feeding in critically ill patients. Crit Care Med.2002; 30:796 -800.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
92. Heyland DK, MacDonald S, Keefe L, Drover JW. Total parenteral nutrition in the critically ill patient: a meta-analysis. JAMA.1998; 280:2013 -2019.[Abstract/Free Full Text]
93. Brennan MF, Pisters PW, Posner M, Quesada O, Shike M. A prospective randomized trial of total parenteral nutrition after major pancreatic resection for malignancy. Ann Surg.1994; 220:436 -444.[Web of Science][Medline] [Order article via Infotrieve]
94. Holter AR, Fischer JE. The effects of perioperative hyperalimentation on complications in patients with carcinoma and weight loss.J Surg Res. 1977;23:31 -34.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
95. Müller JM, Brenner U, Dienst C, Pichlmaier H. Preoperative parenteral feeding in patients with gastrointestinal carcinoma.Lancet. 1982;1:68 -79.[Medline] [Order article via Infotrieve]
96. Sandstrom R, Drott C, Hyltander A, et al. The effect of postoperative intravenous feeding (TPN) on outcome following major surgery evaluated in a randomized study. Ann Surg.1993; 217:185 -195.[Web of Science][Medline] [Order article via Infotrieve]
97. Sax HC, Warner BW, Talamini MA, et al. Early total parenteral nutrition in acute pancreatitis: lack of beneficial effects. Am J Surg. 1987;153:117 -124.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
98. Thompson BR, Julian TB, Stremple JF. Perioperative total parenteral nutrition in patients with gastrointestinal cancer. J Surg Res.1981; 30:497 -500.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
99. Woolfson AM, Smith JA. Elective nutritional support after major surgery: a prospective randomised trial. Clin Nutr.1989; 8:15 -21.[Web of Science][Medline] [Order article via Infotrieve]
100. Abel RM, Fischer JE, Buckley MJ, Barnett GO, Austen WG. Malnutrition in cardiac surgical patients: results of a prospective, randomized evaluation of early postoperative parenteral nutrition. Arch Surg. 1976;111:45 -50.[Abstract/Free Full Text]
101. Reilly J, Mehta R, Teperman L, et al. Nutritional support after liver transplantation: a randomized prospective study. JPEN J Parenter Enteral Nutr. 1990;14:386 -391.[Abstract/Free Full Text]
102. Williams RH, Heatley RV, Lewis MH. Proceedings: a randomized controlled trial of preoperative intravenous nutrition in patients with stomach cancer. Br J Surg.1976; 63:667 .[Web of Science][Medline] [Order article via Infotrieve]
103. Moghissi K, Hornshaw J, Teasdale PR, Dawes EA. Parenteral nutrition in carcinoma of the oesophagus treated by surgery: nitrogen balance and clinical studies. Br J Surg.1977; 64:125 -128.[Web of Science][Medline] [Order article via Infotrieve]
104. Preshaw RM, Attisha RP, Hollingsworth WJ. Randomized sequential trial of parenteral nutrition in healing of colonic anastomoses in man.Can J Surg. 1979;22:437 -439.[Web of Science][Medline] [Order article via Infotrieve]
105. Heatley RV, Williams RH, Lewis MH. Pre-operative intravenous feeding: a controlled trial. Postgrad Med J.1979; 55:541 -545.[Abstract/Free Full Text]
106. Simms JM, Oliver E, Smith JAR. A study of total parenteral nutrition (TPN) in major gastric and esophageal resection for neoplasia.JPEN J Parenter Enteral Nutr.1980; 4:422 .
107. Lim ST, Choa RG, Lam KH, Wong J, Ong GB. Total parenteral nutrition versus gastrostomy in the preoperative preparation of patients with carcinoma of the oesophagus. Br J Surg.1981; 68:69 -72.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
108. Sako K, Loré JM, Kaufman S, Razack MS, Bakamjian V, Reese P. Parenteral hyperalimentation in surgical patients with head and neck cancer: a randomized study. J Surg Oncol.1981; 16:391 -402.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
109. Jensen S. Parenteral nutrition and cancer surgery [abstract].JPEN J Parenter Enteral Nutr.1982; 6: 335. Abstract 112.
110. Moghissi M, Teasdale P, Dench M. Comparison between preoperative enteral (naso-gastric tube) and parenteral feeding in patients with cancer of the oesophagus undergoing surgery [abstract]. JPEN J Parenter Enteral Nutr. 1982;6:335 . Abstract 111.
111. Müller JM, Keller HW, Brenner U, Walter M, Holzmüller W. Indications and effects of preoperative parenteral nutrition. World J Surg. 1986;10:53 -63.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
112. Garden OJ, Smith A, Harris NW, Shenkin A, Sim AJ, Carter DC. The effect of isotonic amino acid infusions on serum proteins and muscle breakdown following surgery. Br J Surg.1983; 70:79 -82.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
113. Bellantone R, Doglietto GB, Bossola M, et al. Preoperative parenteral nutrition in the high risk surgical patient. JPEN J Parenter Enteral Nutr. 1988;12:195 -197.[Abstract/Free Full Text]
114. Smith RC, Hartemink R. Improvement of nutritional measures during preoperative parenteral nutrition in patients selected by the prognostic nutritional index: a randomized controlled trial. JPEN J Parenter Enteral Nutr. 1988;12:587 -591.[Abstract]
115. Meguid MM, Curtas MS, Meguid V, Campos AC. Effects of preoperative TPN on surgical risk: preliminary status report. Br J Clin Pract Suppl. 1988;63:53 -58.[Medline] [Order article via Infotrieve]
116. Bellantone R, Doglietto G, Bossola M, et al. Preoperative parenteral nutrition of malnourished surgical patients. Acta Chir Scand. 1988;154:249 -251.[Web of Science][Medline] [Order article via Infotrieve]
117. Fan ST, Lau WY, Wong KK. Preoperative parenteral nutrition in patients with oesophageal cancer: a prospective randomized clinical trial.Clin Nutr. 1989;8:23 -27.[Web of Science][Medline] [Order article via Infotrieve]
118. Veterans affairs total parenteral nutrition cooperative study group: perioperative total parenteral nutrition in surgical patients. N Engl J Med. 1991;325:525 -532.[Abstract]
119. Von Meyenfeldt MF, Meijerink WJHJ, Rouflart MMJ, Buil-Maassen MTHJ, Soeters PB. Perioperative nutritional support: a randomised clinical trial.Clin Nutr. 1992;11:180 -186.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
120. Fan ST, Lo CM, Lai EC, Chu KM, Liu CL, Wong J. Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. N Engl J Med.1994; 331:1547 -1552.[Abstract/Free Full Text]
121. Xian-Li H, Qing-Jui M, Kian-Guo L, Yan-Kui C, Xi-Lin D. Effect of total parenteral nutrition (TPN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP). Clin Nutr Suppl. 2004;1:43 -47.[CrossRef]
122. Collins JP, Oxby CB, Hill GL. Intravenous aminoacids and intravenous hyperalimentation as protein-sparing therapy after major surgery: a controlled clinical trial. Lancet.1978; 1:788 -791.[Web of Science][Medline] [Order article via Infotrieve]
123. Freund H, Hoover HC Jr, Atamian S, Fischer JE. Infusion of the branched chain amino acids in postoperative patients: anticatabolic properties. Ann Surg.1979; 190:18 -23.[Web of Science][Medline] [Order article via Infotrieve]
124. Yamada N, Koyama H, Hioki K, Yamada T, Yamamoto M. Effect of postoperative total parenteral nutrition (TPN) as an adjunct to gastrectomy for advanced gastric carcinoma. Br J Surg.1983; 70:267 -274.[Web of Science][Medline] [Order article via Infotrieve]
125. Jiménez FJ, Leyba CO, Jiménez LM, Valdecasas MS, Montero JG. Study of hypocaloric peripheral parenteral nutrition in postoperative patients. Clin Nutr.1995; 14:88 -96.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
126. Askanazi J, Hensle TW, Starker PM, et al. Effect of immediate postoperative nutritional support on length of hospitalization. Ann Surg. 1986;203:236 -239.[Web of Science][Medline] [Order article via Infotrieve]
127. Figueras J, Puig P, Rafecas A, et al. Postoperative hypocaloric parenteral nutrition: a study in patients without neoplasm. Acta Chir Scand. 1988;154:435 -438.[Web of Science][Medline] [Order article via Infotrieve]
128. Gys T, Peeters R, Hubens A. The value of short-term peripheral parenteral nutrition after colorectal surgery: a comparative study with conventional postoperative intravenous fluid. Acta Chir Belg.1990; 90:234 -239.[Medline] [Order article via Infotrieve]
129. Hwang TL, Mou SC, Chen MF. The importance of a source of sufficient protein in postoperative hypocaloric partial parenteral nutrition support.JPEN J Parenter Enteral Nutr.1993; 17:254 -256.[Abstract/Free Full Text]
130. Detsky AS, Baker JP, O'Rourke K, Goel V. Perioperative parenteral nutrition: a meta-analysis. Ann Intern Med.1987; 107:195 -203.[Abstract/Free Full Text]
131. Klein S, Kinney J, Jeejeebhoy K, et al. Nutrition support in clinical practice: review of published data and recommendations for future research directions. National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition.JPEN J Parenter Enteral Nutr.1997; 21:133 -156.[Abstract/Free Full Text]
132. Foster GD, Knox LS, Dempsey DT, Mullen JL. Caloric requirements in total parenteral nutrition. J Am Coll Nutr.1987; 6:231 -253.[Abstract]
133. Barr J, Hecht M, Flavin KE, Khorana A, Gould MK. Outcomes in critically ill patients before and after the implementation of an evidence-based nutritional management protocol. Chest.2004; 125:1446 -1457.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
134. Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on the outcome of critically ill mechanically ventilated medical patients.Chest. 2006;129:960 -967.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
135. Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ; Southwestern Ontario Critical Care Research Network. Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). CMAJ.2004; 170:197 -204.[Abstract/Free Full Text]
136. Ziegler TR, Smith RJ, O'Dwyer ST, Demling RH, Wilmore DW. Increased intestinal permeability associated with infection in burn patients.Arch Surg. 1988;123:1313 -1319.[Abstract/Free Full Text]
137. Chiarelli AG, Ferrarello S, Piccioli A, et al. Total enteral nutrition versus mixed enteral and parenteral nutrition in patients in an intensive care unit. Minerva Anestesiol.1996; 62:1 -7.[Medline] [Order article via Infotrieve]
138. Bauer P, Charpentier C, Bouchet C, Nace L, Raffy F, Gaconnet N. Parenteral with enteral nutrition in the critically ill. Intensive Care Med. 2000;26:893 -900.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
139. Herndon DN, Stein MD, Rutan TC, Abston S, Linares H. Failure of TPN supplementation to improve liver function, immunity, and mortality in thermally injured patients. J Trauma.1987; 27:195 -204.[Web of Science][Medline] [Order article via Infotrieve]
140. Herndon DN, Barrow RE, Stein M, et al. Increased mortality with intravenous supplemental feeding in severely burned patients. J Burn Care Rehabil. 1989;10:309 -313.[Medline] [Order article via Infotrieve]
141. Stroud M. Protein and the critically ill: do we know what to give?Proc Nutr Soc. 2007;66:378 -383.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
142. Choban PS, Dickerson RN. Morbid obesity and nutrition support: is bigger different? Nutr Clin Pract.2005; 20:480 -487.[Abstract/Free Full Text]
143. Elamin EM. Nutritional care of the obese intensive care unit patient. Curr Opin Crit Care.2005; 11:300 -303.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
144. McClave SA, Sexton LK, Spain DA, et al. Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. Crit Care Med. 1999;27:1252 -1256.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
145. Jenkins ME, Gottschlich MM, Warden GD. Enteral feeding during operative procedures in thermal injuries. J Burn Care Rehabil.1994; 15:199 -205.[CrossRef][Medline] [Order article via Infotrieve]
146. Pinilla JC, Samphire J, Arnold C, Liu L, Thiessen B. Comparison of gastrointestinal tolerance to two enteral feeding protocols in critically ill patients: a prospective, randomized controlled trial. JPEN J Parenter Enteral Nutr. 2001;25:81 -86.[Abstract/Free Full Text]
147. Montejo JC, Minambres E, Bordeje L, et al. Gastric residual volume during enteral nutrition in ICU patients: the REGANE study. Intensive Care Med. 2009; in press.
148. Tarling MM, Toner CC, Withington PS, Baxter MK, Whelpton R, Goldhill DR. A model of gastric emptying using paracetamol absorption in intensive care patients. Intensive Care Med.1997; 23:256 -260.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
149. Landzinski J, Kiser TH, Fish DN, Wischmeyer PE, MacLaren R. Gastric motility function in critically ill patients tolerant vs intolerant to gastric nutrition. JPEN J Parenter Enteral Nutr.2008; 32:45 -50.[Abstract/Free Full Text]
150. Cohen J, Aharon A, Singer P. The paracetamol absorption test: a useful addition to the enteral nutrition algorithm? Clin Nutr.2000; 19:233 -236.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
151. McClave SA, Lukan JK, Stefater JA, et al. Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients.Crit Care Med. 2005;33:324 -330.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
152. McClave SA, DeMeo MT, DeLegge MH, et al. North American summit on aspiration in the critically ill patient: consensus statement. JPEN J Parenter Enteral Nutr.2002; 26(6 Suppl):S80 -S85.[Abstract/Free Full Text]
153. Adam S, Batson S. A study of problems associated with the delivery of enteral feed in critically ill patients in five ICUs in the UK.Intensive Care Med.1997; 23:261 -266.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
154. Spain DA, McClave SA, Sexton LK, et al. Infusion protocol improves delivery of enteral tube feeding in the critical care unit. JPEN J Parenter Enteral Nutr. 1999;23:288 -292.[Abstract/Free Full Text]
155. Torres A, el-Ebiary M, Gonzalez J, et al. Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation.Am Rev Respir Dis.1993; 148:352 -357.[Web of Science][Medline] [Order article via Infotrieve]
156. Bonten MJ, Gaillard CA, van Tiel FH, Smeets HG, van der Geest S, Stobberingh EE. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest.1994; 105:878 -884.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
157. Pingleton SK, Hinthorn DR, Liu C. Enteral nutrition in patients receiving mechanical ventilation: multiple sources of tracheal colonization include the stomach. Am J Med.1986; 80:827 -832.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
158. Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet.1999; 354:1851 -1858.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
159. van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH, et al. Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study. Crit Care Med. 2006;34:396 -402.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
160. Ibrahim EH, Mehringer L, Prentice D, et al. Early versus late enteral feeding of mechanically ventilated patients: results of a clinical trial. JPEN J Parenter Enteral Nutr.2002; 26:174 -181.[Abstract/Free Full Text]
161. Bonten MJ, Gaillard CA, van der Hulst R, et al. Intermittent enteral feeding: the influence on respiratory and digestive tract colonization in mechanically ventilated intensive-care-unit patients. Am J Respir Crit Care Med. 1996;154:394 -399.[Abstract]
162. Steevens EC, Lipscomb AF, Poole GV, Sacks GS. Comparison of continuous vs intermittent nasogastric enteral feeding in trauma patients: perceptions and practice. Nutr Clin Pract.2002; 17:118 -122.[Abstract/Free Full Text]
163. Hiebert JM, Brown A, Anderson RG, Halfacre S, Rodeheaver GT, Edlich RF. Comparison of continuous vs intermittent tube feedings in adult burn patients. JPEN J Parenter Enteral Nutr.1981; 5:73 -75.[Abstract/Free Full Text]
164. Kocan MJ, Hickisch SM. A comparison of continuous and intermittent enteral nutrition in NICU patients. J Neurosci Nurs.1986; 18:333 -337.[Medline] [Order article via Infotrieve]
165. Ciocon JO, Galindo-Ciocon DJ, Tiessen C, Galindo D. Continuous compared with intermittent tube feeding in the elderly. JPEN J Parenter Enteral Nutr. 1992;16:525 -528.[Abstract/Free Full Text]
166. Booth CM, Heyland DK, Paterson WG. Gastrointestinal promotility drugs in the critical care setting: a systematic review of the evidence.Crit Care Med. 2002;30:1429 -1435.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
167. Yavagal DR, Karnad DR, Oak JL. Metoclopramide for preventing pneumonia in critically ill patients receiving enteral tube feeding: a randomized controlled trial. Crit Care Med.2000; 28:1408 -1411.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
168. Berne JD, Norwood SH, McAuley CE, et al. Erythromycin reduces delayed gastric emptying in critically ill trauma patients: a randomized, controlled trial. J Trauma.2002; 53:422 -425.[Web of Science][Medline] [Order article via Infotrieve]
169. Meissner W, Dohrn B, Reinhart K. Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia. Crit Care Med.2003; 31:776 -780.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
170. DeRiso AJ, Ladowski JS, Dillon TA, Justice JW, Peterson AC. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest.1996; 109:1556 -1561.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
171. Houston S, Hougland P, Anderson JJ, LaRocco M, Kennedy V, Gentry LO. Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery.Am J Crit Care. 2002;11:567 -570.[Abstract/Free Full Text]
172. Zack JE, Garrison T, Trovillion E, et al. Effect of an education program aimed at reducing the occurrence of ventilator-associated pneumonia.Crit Care Med. 2002;30:2407 -2412.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
173. Simmons-Trau D, Cenek P, Counterman J, Hockenbury D, Litwiller L. Reducing VAP with 6 Sigma. Nurs Manage.2004; 35:41 -45.[Medline] [Order article via Infotrieve]
174. Kollef MH. Prevention of hospital-associated pneumonia and ventilator-associated pneumonia. Crit Care Med.2004; 32:1396 -1405.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
175. Maloney JP, Ryan TA. Detection of aspiration in enterally fed patients: a requiem for bedside monitors of aspiration. JPEN J Parenter Enteral Nutr. 2002;26(6 Suppl):S34 -S41.[Free Full Text]
176. Kohn-Keeth C, Frankel E. Taking blue dye out of tube feedings.Nursing. 2004;34:14 .
177. Metheny NA, Clouse RE. Bedside methods for detecting aspiration in tube-fed patients. Chest.1997; 111:724 -731.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
178. Kenneally C, Rosini JM, Skrupky LP, et al. An analysis of thirty-day mortality for clostridium difficile-associated disease in the ICU setting. Chest. 2007;132:418 -424.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
179. Maroo S, Lamont JT. Recurrent clostridium difficile.Gastroenterology. 2006;130:1311 -1316.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
180. Consensus recommendations from the US summit on immune-enhancing enteral therapy. JPEN J Parenter Enteral Nutr.2001; 25:S61 -S62.[Free Full Text]
181. Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg. 1999;229:467 -477.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
182. Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med.1999; 27:2799 -2805.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
183. Martindale RG, Cresci GA. The use of immune enhancing diet in head injury. JPEN J Parenter Enteral Nutr.2001; 25(2 Suppl):S27 -S28.[Free Full Text]
184. Cerra FB, Lehman S, Konstantinides N, Konstantinides F, Shronts EP, Holman R. Effect of enteral nutrient on in vitro tests of immune function in ICU patients: a preliminary report. Nutrition.1990; 6:84 -87.[Web of Science][Medline] [Order article via Infotrieve]
185. Gottschlich MM, Jenkins M, Warden GD, et al. Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. JPEN J Parenter Enteral Nutr.1990; 14:225 -236.[Abstract/Free Full Text]
186. Brown RO, Hunt H, Mowatt-Larssen CA, Wojtysiak SL, Henningfield MF, Kudsk KA. Comparison of specialized and standard enteral formulas in trauma patients. Pharmacotherapy.1994; 14:314 -320.[Web of Science][Medline] [Order article via Infotrieve]
187. Moore FA, Moore EE, Kudsk KA, et al. Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding. J Trauma. 1994;37:607 -615.[Web of Science][Medline] [Order article via Infotrieve]
188. Bower RH, Cerra FB, Bershadsky B, et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med.1995; 23:436 -449.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
189. Kudsk KA, Minard G, Croce MA, et al. A randomized trial of isonitrogenous enteral diets after severe trauma: an immune-enhancing diet reduces septic complications. Ann Surg.1996; 224:531 -540.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
190. Engel JM, Menges T, Neuhauser C, Schaefer B, Hempelmann G. Effects of various feeding regimens in multiple trauma patients on septic complications and immune parameters. Anasthesiol Intensivmed Notfallmed Schmerzther. 1997;32:234 -239.[Web of Science][Medline] [Order article via Infotrieve]
191. Mendez C, Jurkovich GJ, Garcia I, Davis D, Parker A, Maier RV. Effects of an immune-enhancing diet in critically injured patients. J Trauma. 1997;42:933 -940.[Web of Science][Medline] [Order article via Infotrieve]
192. Rodrigo Casanova MP, Garcia Pena JM. The effect of the composition of the enteral nutrition on infection in the critical patient. Nutr Hosp. 1997;12:80 -84.[Medline] [Order article via Infotrieve]
193. Saffle JR, Wiebke G, Jennings K, et al. Randomized trial of immune-enhancing enteral nutrition in burn patients. J Trauma.1997; 42:793 -802.[Web of Science][Medline] [Order article via Infotrieve]
194. Weimann A, Bastian L, Bischoff WE, et al. Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma. Nutrition.1998; 14:165 -172.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
195. Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Guy's Hospital Intensive Care Group. Crit Care Med. 1998;26:1164 -1172.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
196. Galban C, Montejo JC, Mesejo A, et al. An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med.2000; 28:643 -648.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
197. Caparros T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet: the effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr. 2001;25:299 -308.[Abstract/Free Full Text]
198. Conejero R, Bonet A, Grau T, et al. Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study.Nutrition. 2002;18:716 -721.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
199. Dent DL, Heyland DK, Levy H, et al. Immunonutrition may increase mortality in critically ill patients with pneumonia: results of a randomized trial. Crit Care Med.2003; 30:A17 .
200. Bertolini G, Iapichino G, Radrizzani D, et al. Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicentre clinical trial. Intensive Care Med.2003; 29:834 -840.[Web of Science][Medline] [Order article via Infotrieve]
201. Chuntrasakul C, Siltham S, Sarasombath S, et al. Comparison of a immunonutrition formula enriched arginine, glutamine and omega-3 fatty acid, with a currently high-enriched enteral nutrition for trauma patients. J Med Assoc Thai. 2003;86:552 -561.[Medline] [Order article via Infotrieve]
202. Tsuei BJ, Bernard AC, Barksdale AR, Rockich AK, Meier CF, Kearney PA. Supplemental enteral arginine is metabolized to ornithine in injured patients. J Surg Res.2005; 123:17 -24.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
203. Kieft H, Roos A, Bindels A, et al. Clinical outcome of an immune enhancing diet in a heterogenous intensive care population. Intensive Care Med. 2005;31:524 -532.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
204. Wibbenmeyer LA, Mitchell MA, Newel IM, et al. Effect of a fish oil and arginine-fortified diet in thermally injured patients. J Burn Care Res. 2006;27:694 -702.[Web of Science][Medline] [Order article via Infotrieve]
205. Popovic PJ, Zeh HJ III, Ochoa JB. Arginine and immunity. J Nutr. 2007;137(6 Suppl 2): 1681S-1686S.[Abstract/Free Full Text]
206. Calo L, Bianconi L, Colivicchi F, et al. N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol.2005; 45:1723 -1728.[Abstract/Free Full Text]
207. Gadek JE, DeMichele SJ, Karlstad MD, et al. Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Crit Care Med. 1999;27:1409 -1420.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
208. Singer P, Theilla M, Fisher H, Gibstein L, Grozovski E, Cohen J. Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury.Crit Care Med. 2006;34:1033 -1038.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
209. Pontes-Arruda A, Aragao AM, Albuquerque JD. Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock.Crit Care Med. 2006;34:2325 -2333.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
210. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA.2001; 286:944 -953.[Abstract/Free Full Text]
211. Montejo JC, Zarazaga A, Lopez-Martinez J, et al. Immunonutrition in the intensive care unit: a systematic review and consensus statement.Clin Nutr. 2003;22:221 -233.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
212. Waitzberg DL, Saito H, Plank LD, et al. Postsurgical infections are reduced with specialized nutrition support. World J Surg.2006; 30:1592 -1604.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
213. Heyland DK, Novak F. Immunonutrition in the critically ill patient: more harm than good? JPEN J Parenter Enteral Nutr.2001; 25:S51 -S55.[Free Full Text]
214. Zhou M, Martindale RG. Arginine in the critical care setting.J Nutr. 2007;137(6 Suppl 2): 1687S-1692S.[Abstract/Free Full Text]
215. Luiking YC, Poeze M, Preiser J, Deutz N, et al. L-arginine infusion in severely septic patients does not enhance protein nitrosylation or haemodynamic instability. e-SPEN.2006; 1:14 -15.
216. Edes TE, Walk BE, Austin JL. Diarrhea in tube-fed patients: feeding formula not necessarily the cause. Am J Med.1990; 88:91 -93.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
217. Alverdy J, Zaborina O, Wu L. The impact of stress and nutrition on bacterial-host interactions at the intestinal epithelial surface. Curr Opin Clin Nutr Metab Care. 2005;8:205 -209.[Web of Science][Medline] [Order article via Infotrieve]
218. Arvans DL, Vavricka SR, Ren H, et al. Luminal bacterial flora determines physiological expression of intestinal epithelial cyto-protective heat shock proteins 25 and 72. Am J Physiol Gastrointest Liver Physiol. 2005;288:G696 -G704.[Abstract/Free Full Text]
219. Sartor RB. Microbial and dietary factors in the pathogenesis of chronic, immune-mediated intestinal inflammation. Adv Exp Med Biol. 2006;579:35 -54.[Web of Science][Medline] [Order article via Infotrieve]
220. Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology.2007; 132:562 -575.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
221. Bengmark S. Bioecologic control of inflammation and infection in critical illness. Anesthesiol Clin.2006; 24:299 -323.[CrossRef][Medline] [Order article via Infotrieve]
222. Rayes N, Seehofer D, Theruvath T, et al. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation: a randomized, double-blind trial. Am J Transplant.2005; 5:125 -130.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
223. Rayes N, Seehofer D, Hansen S, et al. Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients. Transplantation.2002; 74:123 -127.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
224. Rayes N, Seehofer D, Theruvath T, et al. Effect of enteral nutrition and synbiotics on bacterial infection rates after pylorus-preserving pancreatoduodenectomy: a randomized, double-blind trial. Ann Surg. 2007;246:36 -41.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
225. Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg.2006; 30:1848 -1855.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
226. Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. JPEN J Parenter Enteral Nutr. 2007;31:119 -126.[Abstract/Free Full Text]
227. Oláh A, Belágyi T, Issekutz A, Gamal ME, Bengmark S. Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis. Br J Surg. 2002;89:1103 -1107.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
228. Oláh A, Belagyi T, Poto L, Romics L Jr, Bengmark S. Synbiotic control of inflammation and infection in severe acute pancreatitis: a prospective, randomized, double blind study.Hepatogastroenterology.2007; 54:590 -594.[Medline] [Order article via Infotrieve]
229. Besselink MG, van Santvoort HC, Buskens E, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet.2008; 371:651 -659.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
230. Berger MM, Spertini F, Shenkin A, et al. Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial. Am J Clin Nutr.1998; 68:365 -371.[Abstract]
231. Nathens AB, Neff MJ, Jurkovich GJ, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients.Ann Surg. 2002;236:814 -822.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
232. Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med.2005; 31:327 -337.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
233. Crimi E, Liguori A, Condorelli M, et al. The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: a prospective, randomized, double-blind, placebo-controlled trial. Anesth Analg. 2004;99:857 -863.[Abstract/Free Full Text]
234. Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in intensive care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med.2007; 35:118 -126.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
235. Jones C, Palmer TE, Griffiths RD. Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition.Nutrition. 1999;15:108 -115.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
236. Hall JC, Dobb G, Hall J, de Sousa R, Brennan L, McCauley R. A prospective randomized trial of enteral glutamine in critical illness.Intensive Care Med.2003; 29:1710 -1716.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
237. Garrel DR, Patenaude J, Nedelec B, et al. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003;31:2444 -2449.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
238. Houdijk AP, Rijnsburger ER, Jansen J, et al. Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet.1998; 352:772 -776.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
239. Brantley S, Pierce J. Effects of enteral glutamine on trauma patients [abstract]. Nutr Clin Pract.2000; 15: S13. Abstract P0095.[CrossRef]
240. Zhou YP, Jiang ZM, Sun YH, Wang XR, Ma EL, Wilmore D. The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.JPEN J Parenter Enteral Nutr.2003; 27:241 -245.[Abstract/Free Full Text]
241. Peng X, Yan H, You Z, Wang P, Wang S. Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns.2004; 30:135 -139.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
242. Spapen H, Diltoer M, Van Malderen C, Opdenacker G, Suys E, Huyghens L. Soluble fiber reduces the incidence of diarrhea in septic patients receiving total enteral nutrition: a prospective, double-blind, randomized, and controlled trial. Clin Nutr.2001; 20:301 -305.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
243. Rushdi TA, Pichard C, Khater YH. Control of diarrhea by fiber-enriched diet in ICU patients on enteral nutrition: a prospective randomized controlled trial. Clin Nutr.2004; 23:1344 -1352.[Web of Science][Medline] [Order article via Infotrieve]
244. Dobb GJ, Towler SC. Diarrhoea during enteral feeding in the critically ill: a comparison of feeds with and without fibre. Intensive Care Med. 1990;16:252 -255.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
245. Scaife CL, Saffle JR, Morris SE. Intestinal obstruction secondary to enteral feedings in burn trauma patients. J Trauma.1999; 47:859 -863.[Web of Science][Medline] [Order article via Infotrieve]
246. McIvor AC, Meguid MM, Curtas S, Warren J, Kaplan DS. Intestinal obstruction from cecal bezoar: a complication of fiber-containing tube feedings. Nutrition.1990; 6:115 -117.[Web of Science][Medline] [Order article via Infotrieve]
247. Ahrens CL, Barletta JF, Kanji S, et al. Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: a randomized, controlled trial. Crit Care Med. 2005;33:2507 -2512.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
248. Battistella FD, Widergren JT, Anderson JT, et al. A prospective, randomized trial of intravenous fat emulsion administration in trauma victims requiring total parenteral nutrition. J Trauma.1997; 43:52 -58.[Web of Science][Medline] [Order article via Infotrieve]
249. Choban PS, Burge JC, Scales D, et al. Hypoenergetic nutrition support in hospitalized obese patients: a simplified method for clinical application. Am J Clin Nutr.1997; 66:546 -550.[Abstract/Free Full Text]
250. McCowen KC, Friel C, Sternberg J, et al. Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications: a randomized clinical trial. Crit Care Med. 2000;28:3606 -3611.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
251. Joban N, Garrel DR, Champoux J, Bernier J. Improved immune functions with administration of a low-fat diet in a burn animal model.Cell Immunol. 2000;206:71 -84.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
252. Garrel DR, Razi M, Lariviere F, et al. Improved clinical status and length of care with low-fat nutrition support in burn patients. JPEN J Parenter Enteral Nutr. 1995;19:482 -491.[Abstract/Free Full Text]
253. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med.2001; 345:1359 -1367.[Abstract/Free Full Text]
254. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med.2006; 354:449 -461.[Abstract/Free Full Text]
255. Devos P, Preiser JC. Current controversies around tight glucose control in critically ill patients. Curr Opin Clin Nutr Metab Care. 2007;10:206 -209.[Web of Science][Medline] [Order article via Infotrieve]
256. Fuentes-Orozco C, Anaya-Prado R, Gonzalez-Ojeda A, et al. L-alanyl-L-glutamine-supplemented parenteral nutrition improves infectious morbidity in secondary peritonitis. Clin Nutr.2004; 23:13 -21.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
257. Zeigler TR, Fernandez-Estivariz C, Griffth P, et al. Parenteral nutrition supplemented with alanyl-glutamine dipeptide decreases infectious morbidity and improves organ function in critically ill post-operative patients: results of a double-blind, randomized, controlled pilot study.Nutrition Week Abstracts.2004; 023:52 .
258. Goeters C, Wenn A, Mertes N, et al. Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med. 2002;30:2032 -2037.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
259. Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition.Nutrition. 1997;13:295 -302.[Web of Science][Medline] [Order article via Infotrieve]
260. Griffiths RD, Allen KD, Andrews FJ, Jones C. Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection.Nutrition. 2002;18:546 -552.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
261. Powell-Tuck J, Jamieson CP, Bettany GE, et al. A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition. Gut. 1999;45:82 -88.[Abstract/Free Full Text]
262. Wischmeyer PE, Lynch J, Liedel J, et al. Glutamine administration reduces gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med. 2001;29:2075 -2080.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
263. Zhou Y-D, Jiang Z-M, Sun Y-H, He G-Z, Shu H. The effects of supplemental glutamine dipeptide on gut integrity and clinical outcomes after major escharectomy in severe burns: a randomized, double blind, controlled clinical trial. Clin Nutr Suppl.2004; 1:55 -60.[CrossRef]
264. Dechelotte P, Hasselmann M, Cynober L, et al. L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med. 2006;34:598 -604.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
265. Heyland D, Drover J, Dhaliwal R; Canadian Clinical Practice Guidelines Committee. Does the addition of glutamine to enteral feeds affect patient mortality? Crit Care Med.2006; 34:2031 -2032.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
266. Schloerb PR. Immune-enhancing diets: products, components, and their rationales. JPEN J Parenter Enteral Nutr.2001; 25(2 Suppl):S3 -S7.[Free Full Text]
267. Washizawa N, Gu LH, Gu L, Openo KP, Jones DP, Ziegler TR. Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr. 2004;28:399 -409.[Abstract/Free Full Text]
268. al-Saady NM, Blackmore CM, Bennett ED. High fat, low carbohydrate, enteral feeding lowers PaCO2 and reduces the period of ventilation in artificially ventilated patients. Intensive Care Med.1989; 15:290 -295.[Web of Science][Medline] [Order article via Infotrieve]
269. Barale F, Verdy S, Boillot A, et al. Calorimetric study of enteral low-carbohydrate diet in patients with respiratory insufficiency and decompensation. Agressologie.1990; 31:77 -79.[Medline] [Order article via Infotrieve]
270. Radrizzani D, Iapichino G. Nutrition and lung function in the critically ill patient. Clin Nutr.1998; 17:7 -10.[Web of Science][Medline] [Order article via Infotrieve]
271. Chassard D, Guiraud M, Gauthier J, Gelas P, Berrada KR, Bouletreau P. Effects of intravenous medium-chain triglycerides on pulmonary gas exchanges in mechanically ventilated patients. Crit Care Med.1994; 22:248 -251.[Web of Science][Medline] [Order article via Infotrieve]
272. Mizock BA. Metabolic derangements in sepsis and septic shock.Crit Care Clin. 2000;16:319 -336.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
273. Marin A, Hardy G. Practical implications of nutritional support during continuous renal replacement therapy. Curr Opin Clin Nutr Metab Care. 2001;4:219 -225.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
274. Cano N, Fiaccadori E, Tesinsky P, et al. ESPEN guidelines on enteral nutrition: adult renal failure. Clin Nutr.2006; 25:295 -310.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
275. Bozfakioglu S. Nutrition in patients with acute renal failure.Nephrol Dial Transplant.2001; 16(suppl 6):21 -22.[Free Full Text]
276. Scheinkestel CD, Kar L, Marshall K, et al. Prospective randomized trial to assess caloric and protein needs of critically ill, anuric, ventilated patients requiring continuous renal replacement therapy.Nutrition. 2003;19:909 -916.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
277. Wooley JA, Btaiche IF, Good KL. Metabolic and nutritional aspects of acute renal failure in critically ill patients requiring continuous renal replacement therapy. Nutr Clin Pract.2005; 20:176 -191.[Abstract/Free Full Text]
278. Bellomo R, Tan HK, Bhonagiri S, et al. High protein intake during continuous hemodiafiltration: impact on amino acids and nitrogen balance.Int J Artif Organs.2002; 25:261 -268.[Web of Science][Medline] [Order article via Infotrieve]
279. Plauth M, Cabre E, Riggio O, et al. ESPEN guidelines on enteral nutrition: liver disease. Clin Nutr.2006; 25:285 -294.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
280. Henkel AS, Buchman AL. Nutritional support in patients with chronic liver disease. Nat Clin Pract Gastroenterol Hepatol.2006; 3:202 -209.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
281. Campillo B, Richardet JP, Bories PN. Validation of body mass index for the diagnosis of malnutrition in patients with liver cirrhosis.Gastroenterol Clin Biol.2006; 30:1137 -1143.[Web of Science][Medline] [Order article via Infotrieve]
282. Florez DA, Aranda-Michel J. Nutritional management of acute and chronic liver disease. Semin Gastrointest Dis.2002; 13:169 -178.[Medline] [Order article via Infotrieve]
283. Aranda-Michel J. Nutrition in hepatic failure and liver transplantation. Curr Gastroenterol Rep.2001; 3:362 -370.[CrossRef][Medline] [Order article via Infotrieve]
284. Sanchez AJ, Aranda-Michel J. Nutrition for the liver transplant patient. Liver Transpl.2006; 12:1310 -1316.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
285. Plevak DJ, DiCecco SR, Wiesner RH, et al. Nutritional support for liver transplantation: identifying caloric and protein requirements.Mayo Clin Proc. 1994;69:225 -230.[Web of Science][Medline] [Order article via Infotrieve]
286. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M; Educational and Clinical Practice Committee, European Society of Parenteral and Enteral Nutrition (ESPEN). ESPEN guidelines for nutrition screening 2002. Clin Nutr. 2003;22:415 -421.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
287. Schutz T, Bechstein WO, Neuhaus P, Lochs H, Plauth M. Clinical practice of nutrition in acute liver failure: a European survey. Clin Nutr. 2004;23:975 -982.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
288. Horst D, Grace ND, Conn HO, et al. Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial.Hepatology. 1984;4:279 -287.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
289. Yoshida T, Muto Y, Moriwaki H, Yamato M. Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis. Gastroenterol Jpn.1989; 24:692 -698.[Medline] [Order article via Infotrieve]
290. Marchesini G, Bianchi G, Merli M, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology.2003; 124:1792 -1801.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
291. Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis.Clin Gastroenterol Hepatol.2005; 3:705 -713.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
292. Sato S, Watanabe A, Muto Y, et al. Clinical comparison of branched-chain amino acid (l-leucine, l-isoleucine, l-valine) granules and oral nutrition for hepatic insufficiency in patients with decompensated liver cirrhosis (LIV-EN study). Hepatol Res.2005; 31:232 -240.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
293. Bradley EL. A clinically based classification system for acute pancreatitis: summary of the international symposium on acute pancreatitis.Arch Surg. 1993;128:586 -590.[Abstract/Free Full Text]
294. Forsmark CE, Baillie J. AGA Institute medical position statement on acute pancreatitis. Gastroenterology.2007; 132:2019 -2021.[CrossRef][Medline] [Order article via Infotrieve]
295. Wilson C, Heath DI, Imrie CW. Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. Br J Surg.1990; 77:1260 -1264.[Web of Science][Medline] [Order article via Infotrieve]
296. Agarwal N, Liebson C. Acute pancreatitis: systemic complications and prognostic assessment. Pract Gastroenterol.1991; 15:22 -32.
297. Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ.2004; 328:1407 .[Abstract/Free Full Text]
298. Cao Y, Xu Y, Lu T, Gao F, Mo Z. Meta-analysis of enteral nutrition versus parenteral nutrition in patients with severe acute pancreatitis.Ann Nutr Metab. 2008;53:268 -275.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
299. Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005;100:432 -439.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
300. Kumar A, Singh N, Prakash S, Saraya A, Joshi YK. Early enteral nutrition in severe acute pancreatitis: a prospective randomized controlled trial comparing nasojejunal and nasogastric routes. J Clin Gastroenterol. 2006;40:431 -434.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
301. Cravo M, Camilo ME, Marques A, Pinto Correia J. Early tube feeding in acute pancreatitis: a prospective study. Clin Nutr.1989; 8(suppl):14 .
302. O'Keefe SJ, Broderick T, Turner M, Stevens S, O'Keefe JS. Nutrition in the management of necrotizing pancreatitis. Clin Gastroenterol Hepatol. 2003;1:315 -321.[CrossRef][Medline] [Order article via Infotrieve]
303. Parekh D, Lawson HH, Segal I. The role of total enteral nutrition in pancreatic disease. S Afr J Surg.1993; 31:57 -61.[Web of Science][Medline] [Order article via Infotrieve]
304. Grant JP, Davey-McCrae J, Snyder PJ. Effect of enteral nutrition on human pancreatic secretions. JPEN J Parenter Enteral Nutr.1987; 11:302 -304.[Abstract/Free Full Text]
305. Harsanyi L, Bodoky G, Pap A. The effect of jejunal nutrition on pancreatic exocrine function. Acta Chir Hung.1992 -93;33:13 -21.[Medline] [Order article via Infotrieve]
306. DeLegge MH, McClave SA, DiSario JA, et al. Ethical and medicolegal aspects of PEG-tube placement and provision of artificial nutritional therapy.Gastrointest Endosc.2005; 62:952 -959.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
307. Van der Riet P, Brooks D, Ashby M. Nutrition and hydration at the end of life: pilot study of a palliative care experience. J Law Med. 2006;14:182 -198.[Medline] [Order article via Infotrieve]

Journal of Parenteral and Enteral Nutrition, Vol. 33, No. 3, 277-316 (2009)
DOI: 10.1177/0148607109335234


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. D. Johnson Assessing Gastric Residual Volumes Crit. Care Nurse, October 1, 2009; 29(5): 72 - 73. [Full Text] [PDF]

				D. S. Seres Evidence-Based Nutrition Support: Is a Recession a Good Thing? Nutr Clin Pract, October 1, 2009; 24(5): 541 - 542. [Full Text] [PDF]

				T. R. Ziegler Parenteral Nutrition in the Critically Ill Patient N. Engl. J. Med., September 10, 2009; 361(11): 1088 - 1097. [Full Text] [PDF]

This Article Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by McClave, S. A. Search for Related Content PubMed PubMed Citation Articles by McClave, S. A. Social Bookmarking                         What's this?