Clinical Nutrition and Gastroenterology

Total parenteral nutrition promotes bacterial translocation from the gut

1989-06-01

THE MAINTENANCE NEED FOR WATER IN PARENTERAL FLUID THERAPY

1957-05-01

It is generally agreed that the maintenance requirements for water of individuals is determined by their caloric expenditure. By means of the following formulae, the caloric expenditure of hospitalized patients … It is generally agreed that the maintenance requirements for water of individuals is determined by their caloric expenditure. By means of the following formulae, the caloric expenditure of hospitalized patients can be determined from weight alone. For weights ranging from 0 to 10 kg, the caloric expenditure is 100 cal/kg/day; from 10 to 20 kg the caloric expenditure is 1000 cal plus 50 cal/kg for each kilogram of body weight more than 10; over 20 kg the caloric expenditure is 1500 cal plus 20 cal/kg for each kilogram more than 20. Maintenance requirements for water depend upon insensible loss of water and renal loss. An allowance of 50 ml/100 cal/day will replace insensible loss of water, and 66.7 ml/100 cal/day will replace the average renal loss so that the total requirement is 116.7 ml/100 cal/day. As water of oxidation will supply approximately 16.7 ml/100 cal/day, the remaining 100 ml/100 cal/day must be supplied to meet the remaining water losses of patients on parenteral fluid therapy. Possible exceptions to this figure are discussed. Maintenance requirements of sodium, chloride and potassium are 3.0, 2.0 and 2.0 mEq/100 cal/day, respectively.

Enteral compared with parenteral nutrition: a meta-analysis

2001-10-01

Carol Braunschweig , Paul S. Levy , Patricia Sheean +1 more

ESPGHAN and ESPEN Guidelines Paediatric Parenteral Nutrition ‐ Annex: List of Products

2005-10-27

Berthold Koletzko , Olivier Goulet , J.N. Hunt +2 more

BACKGROUNDThese Guidelines for Paediatric Parenteral Nutrition have been developed as a mutual project of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN; www.espghan.org) and the European Society for … BACKGROUNDThese Guidelines for Paediatric Parenteral Nutrition have been developed as a mutual project of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN; www.espghan.org) and the European Society for Clinical Nutrition and Metabolism (ESPEN; www.espen.org). T

ESPEN Guidelines on Parenteral Nutrition: Intensive care

2009-06-10

Pierre Singer , Mette M. Berger , Greet Van den Berghe +7 more

Benefits of Immediate Jejunostomy Feeding after Major Abdominal Trauma???A Prospective, Randomized Study

1986-10-01

Ernest E. Moore , Todd N. Jones

Benefits of immediate postinjury nutritional support remain ill defined. Seventy-five consecutive patients undergoing emergent celiotomy with an abdominal trauma index (A.T.I.) > 15 were randomized prospectively to a control group … Benefits of immediate postinjury nutritional support remain ill defined. Seventy-five consecutive patients undergoing emergent celiotomy with an abdominal trauma index (A.T.I.) > 15 were randomized prospectively to a control group (no supplemental nutrition during first 5 days) or enteral-fed group. The enteral patients had a needle catheter jejunostomy (N.C.J.) placed at laparotomy with the constant infusion of an elemental diet (Vivonex HN) begun at 18 hours and advanced to 3,000 ml/day (3,000 kcal, 20 gm N2) within 72 hours. Control and enteral-fed groups were comparable with respect to demographic features, trauma mechanism, shock, colon injury, splenectomy, A.T.I., and initial nutritional assessment. Twenty (63%) of the enteral patients were maintained on the elemental diet > 5 days; four (12%) needed total parenteral nutrition (T.P.N.). Nine (29%) of the control patients required T.P.N. Nitrogen balance was markedly improved (p < 0.001) in the enteral-fed group. Although visceral protein markers and overall complication rate were not significantly different, septic morbidity was greater (p < 0.025) in the control group (abdominal infection in seven and pneumonia in two) compared to the enteral-fed patients (abdominal abscess in three). Analysis of patients with A.T.I. 15—40 disclosed sepsis in seven (26%) of the control versus one (4%) of the enteral-fed group (p < 0.01). Our clinical experience demonstrates the feasibility of immediate postoperative enteral feeding via N.C.J. after major abdominal trauma, and suggests this early nutrition reduces septic complications in critically injured patients.

Gastrostomy without laparotomy: A percutaneous endoscopic technique

1980-12-01

Michael W.L. Gauderer , Jeffrey L. Ponsky , Robert J. Izant

Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients

2005-05-18

Stéphane Villet , René Chiolero , Marc Bollmann +4 more

Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients

2003-09-01

D. Heyland , Rupinder Dhaliwal , JW Drover +2 more

OBJECTIVE: This study was conducted to develop evidence‐based clinical practice guidelines for nutrition support (ie, enteral and parenteral nutrition) in mechanically ventilated critically ill adults. OPTIONS: The following interventions were … OBJECTIVE: This study was conducted to develop evidence‐based clinical practice guidelines for nutrition support (ie, enteral and parenteral nutrition) in mechanically ventilated critically ill adults. OPTIONS: The following interventions were systematically reviewed for inclusion in the guidelines: enteral nutrition (EN) versus parenteral nutrition (PN), early versus late EN, dose of EN, composition of EN (protein, carbohydrates, lipids, immune‐enhancing additives), strategies to optimize delivery of EN and minimize risks (ie, rate of advancement, checking residuals, use of bedside algorithms, motility agents, small bowel versus gastric feedings, elevation of the head of the bed, closed delivery systems, probiotics, bolus administration), enteral nutrition in combination with supplemental PN, use of PN versus standard care in patients with an intact gastrointestinal tract, dose of PN and composition of PN (protein, carbohydrates, IV lipids, additives, vitamins, trace elements, immune enhancing substances), and the use of intensive insulin therapy. OUTCOMES: The outcomes considered were mortality (intensive care unit [ICU], hospital, and long‐term), length of stay (ICU and hospital), quality of life, and specific complications. EVIDENCE: We systematically searched MEDLINE and CINAHL (cumulative index to nursing and allied health), EMBASE, and the Cochrane Library for randomized controlled trials and meta‐analyses of randomized controlled trials that evaluated any form of nutrition support in critically ill adults. We also searched reference lists and personal files, considering all articles published or unpublished available by August 2002. Each included study was critically appraised in duplicate using a standard scoring system. VALUES: For each intervention, we considered the validity of the randomized trials or meta‐analyses, the effect size and its associated confidence intervals, the homogeneity of trial results, safety, feasibility, and the economic consequences. The context for discussion was mechanically ventilated patients in Canadian ICUs. BENEFITS, HARMS, AND COSTS: The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients (reduced mortality and ICU stay). Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions. SUMMARIES OF EVIDENCE AND RECOMMENDATIONS: When considering nutrition support in critically ill patients, we strongly recommend that EN be used in preference to PN. We recommend the use of a standard, polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU, that patients be cared for in the semirecumbent position, and that arginine‐containing enteral products not be used. Strategies to optimize delivery of EN (starting at the target rate, use of a feeding protocol using a higher threshold of gastric residuals volumes, use of motility agents, and use of small bowel feeding) and minimize the risks of EN (elevation of the head of the bed) should be considered. Use of products with fish oils, borage oils, and antioxidants should be considered for patients with acute respiratory distress syndrome. A glutamine‐enriched formula should be considered for patients with severe burns and trauma. When initiating EN, we strongly recommend that PN not be used in combination with EN. When PN is used, we recommend that it be supplemented with glutamine, where available. Strategies that maximize the benefit and minimize the risks of PN (hypocaloric dose, withholding lipids, and the use of intensive insulin therapy to achieve tight glycemic control) should be considered. There are insufficient data to generate recommendations in the following areas: use of indirect calorimetry; optimal pH of EN; supplementation with trace elements, antioxidants, or fiber; optimal mix of fats and carbohydrates; use of closed feeding systems; continuous versus bolus feedings; use of probiotics; type of lipids; and mode of lipid delivery. VALIDATION: This guideline was peer‐reviewed and endorsed by official representatives of the Canadian Critical Care Society, Canadian Critical Care Trials Group, Dietitians of Canada, Canadian Association of Critical Care Nurses, and the Canadian Society for Clinical Nutrition. SPONSORS: This guideline is a joint venture of the Canadian Critical Care Society, the Canadian Critical Trials Group, the Canadian Society for Clinical Nutrition, and Dietitians of Canada. The Canadian Critical Care Society and the Institute of Nutrition, Metabolism, and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline.

Amino acids and immune function

2007-04-03

Peng Li , Yulong Yin , Defa Li +2 more

A deficiency of dietary protein or amino acids has long been known to impair immune function and increase the susceptibility of animals and humans to infectious disease. However, only in … A deficiency of dietary protein or amino acids has long been known to impair immune function and increase the susceptibility of animals and humans to infectious disease. However, only in the past 15 years have the underlying cellular and molecular mechanisms begun to unfold. Protein malnutrition reduces concentrations of most amino acids in plasma. Findings from recent studies indicate an important role for amino acids in immune responses by regulating: (1) the activation of T lymphocytes, B lymphocytes, natural killer cells and macrophages; (2) cellular redox state, gene expression and lymphocyte proliferation; and (3) the production of antibodies, cytokines and other cytotoxic substances. Increasing evidence shows that dietary supplementation of specific amino acids to animals and humans with malnutrition and infectious disease enhances the immune status, thereby reducing morbidity and mortality. Arginine, glutamine and cysteine precursors are the best prototypes. Because of a negative impact of imbalance and antagonism among amino acids on nutrient intake and utilisation, care should be exercised in developing effective strategies of enteral or parenteral provision for maximum health benefits. Such measures should be based on knowledge about the biochemistry and physiology of amino acids, their roles in immune responses, nutritional and pathological states of individuals and expected treatment outcomes. New knowledge about the metabolism of amino acids in leucocytes is critical for the development of effective means to prevent and treat immunodeficient diseases. These nutrients hold great promise in improving health and preventing infectious diseases in animals and humans.

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Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients

1993-07-01

A.S.P.E.N. Board

Tube Feeding in Patients With Advanced Dementia

1999-10-13

Thomas E. Finucane , Colleen Christmas , Kathy Travis

Patients with advanced dementia frequently develop eating difficulties and weight loss. Enteral feeding tubes are often used in this situation, yet benefits and risks of this therapy are unclear. We … Patients with advanced dementia frequently develop eating difficulties and weight loss. Enteral feeding tubes are often used in this situation, yet benefits and risks of this therapy are unclear. We searched MEDLINE, 1966 through March 1999, to identify data about whether tube feeding in patients with advanced dementia can prevent aspiration pneumonia, prolong survival, reduce the risk of pressure sores or infections, improve function, or provide palliation. We found no published randomized trials that compare tube feeding with oral feeding. We found no data to suggest that tube feeding improves any of these clinically important outcomes and some data to suggest that it does not. Further, risks are substantial. The widespread practice of tube feeding should be carefully reconsidered, and we believe that for severely demented patients the practice should be discouraged on clinical grounds.

Glutamine supplementation in serious illness: A systematic review of the evidence*

2002-09-01

František Novák , Daren K. Heyland , Alison Avenell +2 more

Objective To examine the relationship between glutamine supplementation and hospital length of stay, complication rates, and mortality in patients undergoing surgery and experiencing critical illness. Data Sources Computerized search of … Objective To examine the relationship between glutamine supplementation and hospital length of stay, complication rates, and mortality in patients undergoing surgery and experiencing critical illness. Data Sources Computerized search of electronic databases and search of personal files, abstract proceedings, relevant journals, and review of reference lists. Study Selection We reviewed 550 titles, abstracts, and articles. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of glutamine vs. standard care on clinical outcomes. Data Extraction We abstracted relevant data on the methodology and outcomes of primary studies in duplicate, independently. Data Synthesis There were 14 randomized trials comparing the use of glutamine supplementation in surgical and critically ill patients. When the results of these trials were aggregated, with respect to mortality, glutamine supplementation was associated with a risk ratio (RR) of 0.78 (95% confidence interval [CI], 0.58–1.04). Glutamine supplementation was also associated with a lower rate of infectious complications (RR, 0.81; 95% CI, 0.64–1.00) and a shorter hospital stay (−2.6 days; 95% CI, −4.5 to −0.7). We examined several a priori–specified subgroups. Although there were no statistically significant subgroup differences detected, there were some important trends. With respect to mortality, the treatment benefit was observed in studies of parenteral glutamine (RR, 0.71; 95% CI, 0.51–0.99) and high-dose glutamine (RR, 0.73; 95% CI, 0.53–1.00) compared with studies of enteral glutamine (RR, 1.08; 95% CI, 0.57–2.01) and low-dose glutamine (RR, 1.02; 95% CI, 0.52–2.00). With respect to hospital length of stay, all of the treatment benefit was observed in surgical patients (−3.5 days; 95% CI, −5.3 to −1.7) compared with critically ill patients (0.9 days; 95% CI, −4.9 to 6.8). Conclusion In surgical patients, glutamine supplementation may be associated with a reduction in infectious complication rates and shorter hospital stay without any adverse effect on mortality. In critically ill patients, glutamine supplementation may be associated with a reduction in complication and mortality rates. The greatest benefit was observed in patients receiving high-dose, parenteral glutamine.

Early Enteral Feeding, Compared With Parenteral, Reduces Postoperative Septic Complications The Results of a Meta-Analysis

1992-08-01

Frederick A. Moore , David V. Feliciano , Richard J. Andrassy +6 more

This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined … This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.

Glutamine and the preservation of gut integrity

1993-05-01

René R. W. J. van der Hulst , M.F. von Meyenfeldt , Nicolaas E.P. Deutz +4 more

Nutrition Needs of Mammalian Cells in Tissue Culture

1955-09-16

Harry Eagle

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Is Glutamine a Conditionally Essential Amino Acid?

2009-04-27

Janet M. Lacey , Douglas W. Wilmore

The nonessential amino acid glutamine has recently been the focus of extensive scientific interest because of its importance in cell and tissue cultures and its physiologic role in animals and … The nonessential amino acid glutamine has recently been the focus of extensive scientific interest because of its importance in cell and tissue cultures and its physiologic role in animals and humans. Glutamine appears to be a unique amino acid, serving as a preferred respiratory fuel for rapidly proliferating cells, such as enterocytes and lymphocytes; a regulator of acid-base balance through the production of urinary ammonia; a carrier of nitrogen between tissues; and an important precursor of nucleic acids, nucleotides, amino sugars, and proteins. Abundant evidence suggests that glutamine may become a "conditionally essential" amino acid in the critically ill. During stress the body's requirements for glutamine appear to exceed the individual's ability to produce sufficient amounts of this amino acid. Provision of supplemental glutamine in specialized enteral or parenteral feeding may enhance nutritional management and augment recovery of the seriously ill while minimizing hospital stay.

TEN versus TPN following Major Abdominal Trauma—Reduced Septic Morbidity

1989-07-01

Frederick A. Moore , Ernest E. Moore , Todd N. Jones +2 more

Recent animal models suggest that enteral feeding (TEN) compared to parenteral nutrition (TPN) improves resistance to infection. This prospective clinical trial examined the impact of early TEN vs. TPN in … Recent animal models suggest that enteral feeding (TEN) compared to parenteral nutrition (TPN) improves resistance to infection. This prospective clinical trial examined the impact of early TEN vs. TPN in the critically injured. Seventy-five patients with an abdominal trauma index (ATI) greater than 15 and less than 40 were randomized at initial laparotomy to receive either TEN (Vivonex TEN) or TPN (Freamine HBC 6.9% and Trophamine 6%); both regimens contained 2.5% fat, 33% branched chain amino acids, and had a calorie to nitrogen ratio of 150:1. TEN was delivered via a needle catheter jejunostomy. Nutritional support was initiated within 12 hours postoperatively in both groups, and infused at a rate sufficient to render the patients in positive nitrogen balance. The study groups (TEN = 29 vs TPN = 30) were comparable in age, injury severity and initial metabolic stress. Jejunal feeding was tolerated unconditionally in 25 (86%) of the TEN group. Nitrogen balance remained equivalent throughout the study period, at day 5 TEN = -0.3 +/- 1.0 vs. TPN 0.1 +/- 0.8 gm/day. Traditional nutritional protein markers (albumin, transferrin, and retinol binding protein) were restored better in the TEN group. Infections developed in 5 (17%) of the TEN patients compared to 11 (37%) of the TPN group. The incidence of major septic morbidity was 3% (1 = abdominal abscess) in the TEN group contrasted to 20% (2 = abdominal abscess, 6 = pneumonia) with TPN. This clinical study demonstrates that TEN is well tolerated in the severely injured, and that early feeding via the gut reduces septic complications in the stressed patient.

Nutritional and metabolic assessment of the hospitalized patient

1977-01-01

George L. Blackburn , Bruce R. Bistrian , Baltej S. Maini +2 more

Early enteral nutrition in acutely ill patients: A systematic review

2001-12-01

Paul E. Marik , Gary P. Zaloga

Objective To evaluate the effect of early enteral nutrition on the outcome of critically ill and injured patients. Data Sources MEDLINE, citation review of relevant primary and review articles, personal … Objective To evaluate the effect of early enteral nutrition on the outcome of critically ill and injured patients. Data Sources MEDLINE, citation review of relevant primary and review articles, personal files, and contact with expert informants. Study Selection Randomized, controlled studies that compared early with delayed enteral nutrition in hospitalized adult postoperative, trauma, head-injured, burn, or medical intensive care unit (ICU) patients. From 161 articles screened, 27 were identified as randomized, controlled trials comparing early with delayed enteral nutrition and were included for data extraction. Of these, 12 were excluded. None of the studies included medical ICU patients. Data Extraction Fifteen studies containing 753 subjects were analyzed. Descriptive and outcome data were extracted independently from the articles by the two reviewers. Main outcome measures were infections, noninfectious complications, length of hospital stay, and mortality. The meta-analysis was performed using the random effects model. Data Synthesis Early enteral nutrition was associated with a significantly lower incidence of infections (relative risk reduction, 0.45; 95% confidence interval, 0.30–0.66;p = .00006; test for heterogeneity, p = .049) and a reduced length of hospital stay (mean reduction of 2.2 days; 95% confidence interval, 0.81–3.63 days;p = .004; test for heterogeneity, p = .0012). There were no significant differences in mortality or noninfectious complications between the two groups of patients. Conclusions The results of this meta-analysis support the experimental data demonstrating the benefit of the early initiation of enteral nutrition. The results of this meta-analysis must, however, be interpreted with some caution because of the significant heterogeneity between studies.

Should Immunonutrition Become Routine in Critically Ill Patients?

2001-08-22

Daren K. Heyland , František Novák , John Drover +3 more

ContextSeveral nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear.ObjectiveTo examine … ContextSeveral nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear.ObjectiveTo examine the relationship between enteral nutrition supplemented with immune-enhancing nutrients and infectious complications and mortality rates in critically ill patients.Data SourcesThe databases of MEDLINE, EMBASE, Biosis, and CINAHL were searched for articles published from 1990 to 2000. Additional data sources included the Cochrane Controlled Trials Register from 1990 to 2000, personal files, abstract proceedings, and relevant reference lists of articles identified by database review.Study SelectionA total of 326 titles, abstracts, and articles were reviewed. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of enteral nutrition supplemented with some combination of arginine, glutamine, nucleotides, and omega-3 fatty acids on infectious complication and mortality rates compared with standard enteral nutrition, and included clinically important outcomes, such as mortality.Data ExtractionMethodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently.Data SynthesisTwenty-two randomized trials with a total of 2419 patients compared the use of immunonutrition with standard enteral nutrition in surgical and critically ill patients. With respect to mortality, immunonutrition was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval [CI], 0.93-1.31). Immunonutrition was associated with lower infectious complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant heterogeneity across studies, we examined several a priori subgroup analyses. We found that studies using commercial formulas with high arginine content were associated with a significant reduction in infectious complications and a trend toward a lower mortality rate compared with other immune-enhancing diets. Studies of surgical patients were associated with a significant reduction in infectious complication rates compared with studies of critically ill patients. In studies of critically ill patients, studies with a high-quality score were associated with increased mortality and a significant reduction in infectious complication rates compared with studies with a low-quality score.ConclusionImmunonutrition may decrease infectious complication rates but it is not associated with an overall mortality advantage. However, the treatment effect varies depending on the intervention, the patient population, and the methodological quality of the study.

ESPEN Guidelines on Parenteral Nutrition: Surgery

2009-05-22

Marco Braga , Olle Ljungqvist , Peter B. Soeters +3 more

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

2016-01-16

Beth Taylor , Stephen A. McClave , Robert G. Martindale +7 more

PRELIMINARY REMARKS (INTENT OF GUIDELINES) A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science … PRELIMINARY REMARKS (INTENT OF GUIDELINES) A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, 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 current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint "harmonization process" with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies. Literature searches were then performed using key words (critically ill, critical care, intensive care, nutrition, enteral, parenteral, tube feeding, and those related to assigned topics such as pancreatitis, sepsis, etc.) to evaluate the quality of evidence supporting a response to those questions, which were then used to derive a subsequent treatment recommendation. The literature search included MEDLINE, PubMed, Cochrane Database of Systemic Reviews, the National Guidelines Clearing House and an Internet search using the Google search engine for scholarly articles through an end date of December 31, 2013 (including ePub publications). While preference was given to RCTs, other forms of resource material were used to support the response, including nonrandomized cohort trials, prospective observational studies, and retrospective case series. Use of publications was limited to full-text articles available in English on adult humans. For all included RCTs, two readers completed data abstraction forms (DAFs) examining the data and assessing the quality of the research methodology to produce a shared evaluation achieved by consensus for each study (example of DAF provided in the supplemental data, Supplemental Digital Content 1, https://links.lww.com/CCM/B571). DAFs were constructed only for RCTs. When the strongest available evidence was a published meta-analysis, the studies from the meta-analysis were used to determine the quality of the evidence and assessed by two evidence assessors. The data from included trials were entered into Review Manager 5.2 software to create forest plots aggregating the effect size for each intervention and outcome (3). The key forest plots supporting the recommendation are included throughout the text and in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). No new forest plots were created when a meta-analysis was evaluated. Since release of the 2009 A.S.P.E.N. and SCCM Clinical Guidelines, the concepts of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group have been adopted (4–7). A full description of the methodology has been previously published (4). The data from the Review Manager analysis was uploaded to GRADEPro software (8), where the body of evidence for a given intervention and outcome was evaluated for overall quality. One analyst created each GRADE table that was then independently confirmed by a second analyst. The GRADE tables are provided in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). Due to the inordinately large number of RCTs evaluated, observational studies were critically reviewed, but not utilized to construct the GRADE tables. However, in the few cases where observational studies were the only available evidence in a population, their quality of evidence was reviewed, using GRADE (Table 1). When no RCT or observational study was available to answer a question directly, consensus of the author group on the best clinical practice approach was used, and the recommendation was designated "based on expert consensus."TABLE 1: Type of EvidenceA recommendation for clinical practice was based on both the best available evidence and the risks and benefits to patients. While small author teams developed each recommendation and provided the supporting rationale, a full discussion by the entire author group followed, and every committee member was polled anonymously for their agreement with the recommendation. Achievement of consensus was arbitrarily set at 70% agreement of authors with a particular recommendation. Only one recommendation (H3a) did not meet this level of agreement, with a final consensus of 64%. All other consensus-based recommendations reached a level of agreement of 80% or higher. As with all A.S.P.E.N. and SCCM clinical guidelines, this manuscript was subjected to rigorous peer review by clinical content experts from all the practice disciplines that would use the guidelines, both internal and external to the organizations. A summary of the guidelines is presented in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). A nutrition bundle based on the top guidelines (as voted on by the committee) for the bedside practitioner is presented in Table 2.TABLE 2: Bundle StatementsCONFLICT OF INTEREST All authors completed both an A.S.P.E.N. and SCCM conflict of interest form for copyright assignment and financial disclosure. There was no input or funding from industry, nor were any industry representatives present at any of the committee meetings. DEFINITIONS Nutrition Therapy refers specifically to the provision of either enteral nutrition (EN) by enteral access device and/or parenteral nutrition (PN) by central venous access. Standard therapy (STD) refers to provision of IV fluids, no EN or PN, and advancement to oral diet as tolerated. INTRODUCTION The significance of nutrition in the hospital setting (and especially the ICU) cannot be overstated. Critical illness is typically associated with a catabolic stress state in which patients demonstrate a systemic inflammatory response coupled with complications of increased infectious morbidity, multiple organ dysfunction, prolonged hospitalization, and disproportionate mortality. Over the past three decades, exponential advances have been made in the understanding of the molecular and biological effects of nutrients in maintaining homeostasis in the critically ill population. Traditionally, nutrition support in the critically ill population was regarded as adjunctive care designed to provide exogenous fuels to preserve lean body mass and support the patient throughout the stress response. Recently this strategy has evolved to represent nutrition therapy, in which the feeding is thought to help attenuate the metabolic response to stress, prevent oxidative cellular injury, and favorably modulate immune responses. Improvement in the clinical course of critical illness may be achieved by early EN, appropriate macro- and micronutrient delivery, and meticulous glycemic control. Delivering early nutrition support therapy, primarily by the enteral route, is seen as a proactive therapeutic strategy that may reduce disease severity, diminish complications, decrease LOS in the ICU, and favorably impact patient outcomes. A. NUTRITION ASSESSMENT Question: Does the use of a nutrition risk indicator identify patients who will most likely benefit from nutrition therapy? A1. Based on expert consensus, we suggest a determination of nutrition risk (for example, Nutritional Risk Score [NRS-2002], NUTRIC score) be performed on all patients admitted to the ICU for whom volitional intake is anticipated to be insufficient. High nutrition risk identifies those patients most likely to benefit from early EN therapy. Rationale: Poor outcomes have been associated with inflammation generated by critical illness that leads to deterioration of nutrition status and malnutrition (9). However, malnutrition in the critically ill has always been difficult to define. An international consensus group modified definitions to recognize the impact of inflammation. Objective measures of baseline nutrition status have been described by A.S.P.E.N. and the Academy of Nutrition and Dietetics (10, 11). On the other hand, nutrition risk is easily defined and more readily determined by evaluation of baseline nutrition status and assessment of disease severity. All hospitalized patients are required to undergo an initial nutrition screen within 48 hours of admission. However, patients at higher nutrition risk in an ICU setting require a full nutrition assessment. Many screening and assessment tools are used to evaluate nutrition status, such as the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), the Short Nutritional Assessment Questionnaire (SNAQ), the Malnutrition Screening Tool (MST), and the Subjective Global Assessment (SGA) (12). However, only the NRS-2002 and the NUTRIC score determine both nutrition status and disease severity. Although both scoring systems were based on retrospective analysis, they have been used to define nutrition risk in RCTs in critically ill patients (13–16). Patients at "risk" are defined by an NRS-2002 > 3 and those at "high risk" with a score ≥ 5; or a NUTRIC score ≥ 5 (if interleukin-6 is not included, otherwise ≥ 6) (13, 18). Interleukin-6 is rarely available as a component for the NUTRIC score; therefore, Heyland et al has shown a NUTRIC score ≥ 5 still indicates high nutrition risk (19). Two prospective nonrandomized studies show that patients at high nutrition risk are more likely to benefit from early EN with improved outcome (reduced nosocomial infection, total complications, and mortality) than patients at low nutrition risk (13, 18). While widespread use and supportive evidence is somewhat lacking to date, improvement in these scoring systems may increase their applicability in the future by providing guidance as to the role of EN and PN in the ICU. Question: What additional tools, components or surrogate markers provide useful information when performing nutrition assessments in critically ill adult patients? A2. Based on expert consensus, we suggest that nutritional assessment include an evaluation of comorbid conditions, function of the gastrointestinal (GI) tract, and risk of aspiration. We suggest not using traditional nutrition indicators or surrogate markers, as they are not validated in critical care. Rationale: In the critical care setting, the traditional serum 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 (20). Anthropometrics are not reliable in assessment of nutrition status or adequacy of nutrition therapy (21). Individual levels of calcitonin, C-reactive protein (CRP), IL-1, tumor necrosis factor (TNF), IL-6, and citrulline are still investigational and should not be used as surrogate markers. Ultrasound is emerging as a tool to expediently measure muscle mass and determine changes in muscle tissue at bedside in the ICU, given its ease of use and availability (22, 23). A CT scan provides a precise quantification of skeletal muscle and adipose tissue depots; however it is quite costly unless a scan taken for other purposes is used to determine body composition (24, 25). Both may be valuable future tools to incorporate into nutrition assessment; however, validation and reliability studies in ICU patients are still pending. Assessment of muscle function is still in its infancy. Its measurement, reproducibility, and applicability are still being validated for use in critically ill patients, and may be of value in the future. Question: What is the best method for determining energy needs in the critically ill adult patient? A3a. We suggest that indirect calorimetry (IC) be used to determine energy requirements, when available and in the absence of variables that affect the accuracy of measurement. [Quality of Evidence: Very Low] A3b. Based on expert consensus, in the absence of IC, we suggest that a published predictive equation or a simplistic weight-based equation (25–30 kcal/kg/day) be used to determine energy requirements. (See section Q for obesity recommendations.) Rationale: Clinicians should determine energy requirements in order to establish the goals of nutrition therapy. Energy requirements may be calculated either through simplistic formulas (25–30 kcal/kg/day), published predictive equations, or IC. The applicability of IC may be limited at most institutions by availability and cost. Variables in the ICU that affect the timing and accuracy of IC measurements include the presence of air leaks or chest tubes, supplemental oxygen (e.g., nasal cannula, bilevel positive airway pressure), ventilator settings (fractional inspiratory oxygen and positive end-expiratory pressure), continuous renal replacement therapy (CRRT), anesthesia, physical therapy, and excessive movement (26). More than 200 predictive equations have been published in the literature, with accuracy rates ranging from 40–75% when compared to IC, and no single equation emerges as being more accurate in an ICU (27–32). Predictive equations are less accurate in obese and underweight patients (33–36). Equations derived from testing hospital patients (Penn State, Ireton-Jones, Swinamer) are no more accurate than equations derived from testing normal volunteers (Harris-Benedict, Mifflin St. Jeor) (37). The poor accuracy of predictive equations is related to many non-static variables affecting energy expenditure in the critically ill patient, such as weight, medications, treatments, and body temperature. The only advantage of using weight-based equations over other predictive equations is simplicity. However, in critically ill patients following aggressive volume resuscitation or in the presence of edema or anasarca, clinicians should use dry or usual body weight in these equations. Additional energy provided by dextrose-containing fluids and lipid-based medications such as propofol should be accounted for when deriving nutrition therapy regimens to meet target energy goals. Achieving energy balance as guided by IC measurements compared to predictive equations may lead to more appropriate nutrition intake. While two RCTs (38, 39) that met our inclusion criteria (with data from 161 patients) showed that higher mean intake of energy and protein were provided in IC-directed study patients compared to controls whose nutrition therapy was directed by predictive equations, issues with study design prevent a stronger recommendation for use of IC. In a study of burn patients, use of IC-directed nutrition therapy helped provide the minimal effective intake, avoiding the excesses of overfeeding seen in controls whose therapy was directed by the Curreri formula. Complications between groups (diarrhea and hyperglycemia) were no different, but traditional outcome parameters were not evaluated (38). A second study in general ICU patients used both EN and PN to meet target energy goals determined by IC measurement or a weight-based predictive equation (25 kcal/kg/day) (39). While the IC-directed energy goal was no different than the value obtained by predictive equation (1976 ± 468 vs 1838 ± 468 kcal/day, respectively, p = 0.60), only study patients were monitored vigilantly by an ICU dietitian, while controls were managed by standard of care (less frequent ICU dietitian monitoring), which led to significantly more energy and protein per day in the study patients. The trend toward reduced mortality in study patients compared to controls (RR = 0.63; 95% CI, 0.39–1.02; p = 0.06) is difficult to reconcile in light of their increased morbidity with regard to ICU LOS (17.2 + 14.6 vs 11.7 + 8.4 days, p = 0.04) and duration of mechanical ventilation (16.1 + 14.7 vs 10.5 + 8.3 days, p = 0.03) (38, 39). Whether measured by IC or estimated by predictive equations, energy expenditure should be reevaluated more than once per week, and strategies to optimize energy and protein intake should be used (39, 40). Question: Should protein provision be monitored independently from energy provision in critically ill adult patients? A4. Based on expert consensus, we suggest an ongoing evaluation of adequacy of protein provision be perforMed 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 thus are not easily met by provision of routine enteral formulations (which have a high nonprotein calorie-to-nitrogen ratio [NPC:N]). Patients with suboptimal EN due to frequent interruptions may benefit from protein supplementation. The decision to add protein modules should be based on an ongoing assessment of adequacy of protein intake. Weight-based equations (e.g., 1.2–2.0 g/kg/day) may be used to monitor adequacy of protein provision by comparing the amount of protein delivered to that prescribed, especially when nitrogen balance studies are not available to assess needs (see section C4) (41, 42). Serum protein markers (albumin, prealbumin, transferrin, CRP) are not validated for determining adequacy of protein provision and should not be used in the critical care setting in this manner (20, 43). B. INITIATE EN Question: What is the benefit of early EN in critically ill adult patients compared to withholding or delaying this therapy? B1. We recommend that nutrition support therapy in the form of early EN be initiated within 24–48 hours in the critically ill patient who is unable to maintain volitional intake. [Quality of Evidence: Very Low] 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 (B cells and plasma cells) that 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 (44–46). Adverse change in gut permeability from loss of functional integrity is a dynamic phenomenon that 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 multiple organ dysfunction syndrome (MODS) (45, 46). 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 LOS (47). The specific reasons for providing EN are to maintain gut integrity, modulate stress and the systemic immune response, and attenuate disease severity (44, 47, 48). Additional endpoints of EN therapy may 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. Three previous meta-analyses aggregated data from RCTs comparing early versus delayed EN. One meta-analysis of eight trials by Heyland showed a trend toward reduced mortality (RR = 0.52; 95% CI, 0.25–1.08; p = 0.08) (49), when EN was started within 48 hours compared to delayed initiation of EN started after that point. A second meta-analysis of 12 trials by Marik showed significant reductions in infectious morbidity (RR = 0.45; 95% CI, 0.30–0.66; p = 0.00006) and hospital LOS (mean 2.2 days; 95% CI, 0.81–3.63 days; p = 0.001) when early EN was started on average within 36 hours of ICU admission (50). A third meta-analysis of six trials by Doig showed a significant reduction in pneumonia (OR = 0.31; 95% CI, 0.12–0.78; p = 0.01) and mortality (OR = 0.34; 95% CI, 0.14–0.85; p = 0.02), but no difference in multiple organ failure (MOF) when early EN was started within 24 hours of admission to the ICU, compared to EN started after that point (51). Of an updated meta-analysis of 21 RCTs that met our inclusion criteria comparing the provision of early EN versus delayed EN, all reported on mortality (Figure 1), with 13 reporting on infection (Figure 2). Provision of early EN was associated with a significant reduction in mortality (RR = 0.70; 95% CI, 0.49–1.00; p = 0.05) and infectious morbidity (RR = 0.74; 95% CI, 0.58–0.93, p = 0.01), compared to withholding early EN (delayed EN or STD).Figure 1: Early enteral nutrition (EN) vs delayed EN, mortality.Figure 2: Early enteral nutrition (EN) vs delayed EN, infectious complications.Question: Is there a difference in outcome between the use of EN or PN for adult critically ill patients? B2. We suggest the use of EN over PN in critically ill patients who require nutrition support therapy. [Quality of Evidence: Low to Very Low] Rationale: In the majority of critically ill patients it is practical and safe to use EN instead of PN. The beneficial effects of EN compared to PN are well documented in numerous RCTs involving a variety of patient populations in critical illness, including trauma, burns, head injury, major surgery, and acute pancreatitis (47, 49, 52–54). 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) and ICU LOS. Six previous meta-analyses comparing EN to PN showed significant reductions in infectious morbidity with use of EN (49, 55–59). Non-infective complications (risk difference = 4.9; 95% CI, 0.3–9.5; p = 0.04) and reduced hospital LOS (weighted mean difference [WMD] = 1.20 days; 95% CI, 0.38–2.03; p = 0.004) were seen with use of EN compared to PN in one of the meta-analyses by Peter (57). Five of the meta-analyses showed no difference in mortality between the two routes of nutrition support therapy (49, 55–59). One meta-analysis by Simpson showed a significantly lower mortality (RR = 0.51; 95% CI, 0.27–0.97; p = 0.04) despite a significantly higher incidence of infectious complications (RR = 1.66; 95% CI, 1.09–2.51; p = 0.02) with use of PN compared to EN (59). In 12 studies (53, 58, 60–69) representing 618 patients that met our inclusion criteria, 9 reported on infection (Figure 3), which was shown to be significantly less with EN than PN (RR = 0.56; 95% CI, 0.39–0.79; p < .00001). ICU LOS also was shorter with EN compared to PN by nearly one full day (MD = –0.82; 95% CI, –1.29 to –0.34, p = 0.0007). Hospital LOS and mortality were not significantly different. These differences in outcome from the separate routes of feeding largely reflect findings from older studies and may diminish in the future with improvements in glycemic control, protocolized medical management and new lipid emulsions.Figure 3: Enteral nutrition (EN) vs parenteral nutrition (PN), infectious complications.Question: Is the clinical evidence of contractility (bowel sounds, flatus) required prior to initiating EN in critically ill adult patients? B3. Based on expert consensus, we suggest that, in the majority of MICU and SICU patient populations, while GI contractility factors should be evaluated when initiating EN, overt signs of contractility should not be required prior to initiation of EN. Rationale: The literature supports the concept that bowel sounds and evidence of bowel function, i.e., passing flatus or stool, are not required for initiation of EN. GI dysfunction in the ICU setting occurs in 30–70% of patients, depending on the diagnosis, premorbid condition, ventilation mode, medications, and metabolic state (70). Proposed mechanisms of ICU and postoperative GI dysfunction are related to mucosal barrier disruption, altered motility, atrophy of the mucosa, and reduced mass of GALT. GI intolerance has been variably defined (e.g., absence or abnormal bowel sounds, vomiting, bowel dilatation, diarrhea, GI bleeding, high gastric residual volumes [GRVs], etc.) and appears to occur in up to 50% of patients on mechanical ventilation. Bowel sounds are indicative only of contractility and do not necessarily relate to mucosal integrity, barrier function, or absorptive capacity. The argument for initiating EN regardless of the extent of audible bowel sounds is based on studies (most of which involve critically ill surgical patients) reporting the feasibility and safety of EN within the initial 36–48 hours of admission to the ICU. Nonetheless, reduced or absent bowel sounds may reflect greater disease severity and worsened prognosis. Patients with normal bowel sounds have been shown to have lower ICU mortality than those with hypoactive or absent bowel sounds (11.3% vs 22.6% vs 36.0%, respectively) (71). ICU LOS has been shown to increase with greater number of symptoms of GI intolerance (2.9 days when asymptomatic versus up to 16.8 days with four symptoms of intolerance) (72). Not surprisingly, success of EN delivery is reduced with a greater number of symptoms of GI intolerance. A greater number of signs of intolerance may warrant increased vigilance as EN is started, and may necessitate further clinical evaluation. Question: What is the preferred level of infusion of EN within the GI tract for critically ill patients? How does the level of infusion of EN affect patient outcomes? B4a. We recommend that the level of infusion be diverted lower in the GI tract in those critically ill patients at high risk for aspiration (see section D4) or those who have shown intolerance to gastric EN. [Quality of Evidence: Moderate to High] B4b. Based on expert consensus we suggest that, in most critically ill patients, it is acceptable to initiate EN in the stomach. Rationale: Initiating EN therapy in the stomach is technically easier and may decrease the time to initiation of EN. The choice of level of infusion (i.e., whether the tip of the feeding tube is in the stomach, different segments of the duodenum [D1, D2, D3 or D4], or the jejunum) within the GI tract may be determined by patient selection within ICU practitioners' institutional framework (ease and feasibility of placing small bowel enteral access devices, institutional policies, and

Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool

2011-11-15

Daren K. Heyland , Rupinder Dhaliwal , Xuran Jiang +1 more

Abstract Introduction To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU). Methods A prospective, observational study of patients expected to stay > 24 hours. … Abstract Introduction To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU). Methods A prospective, observational study of patients expected to stay > 24 hours. We collected data for key variables considered for inclusion in the score which included: age, baseline APACHE II, baseline SOFA score, number of comorbidities, days from hospital admission to ICU admission, Body Mass Index (BMI) < 20, estimated % oral intake in the week prior, weight loss in the last 3 months and serum interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) levels. Approximate quintiles of each variable were assigned points based on the strength of their association with 28 day mortality. Results A total of 597 patients were enrolled in this study. Based on the statistical significance in the multivariable model, the final score used all candidate variables except BMI, CRP, PCT, estimated percentage oral intake and weight loss. As the score increased, so did mortality rate and duration of mechanical ventilation. Logistic regression demonstrated that nutritional adequacy modifies the association between the score and 28 day mortality (p = 0.01). Conclusions This scoring algorithm may be helpful in identifying critically ill patients most likely to benefit from aggressive nutrition therapy.

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Functional Amino Acids in Growth, Reproduction, and Health

2010-11-01

Guoyao Wu

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The Harris Benedict equation reevaluated: resting energy requirements and the body cell mass

1984-07-01

Allan M. Roza , H.M. Shizgal

Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial

2012-12-04

Claudia Paula Heidegger , Mette M. Berger , Séverine Graf +5 more

ESPEN Guidelines on Enteral Nutrition: Liver disease

2006-04-01

Mathias Plauth , Eduard Cabré , Oliviero Riggio +7 more

Refeeding syndrome: what it is, and how to prevent and treat it

2008-06-26

Hisham Mehanna , Jamil Moledina , Jane Travis

Refeeding syndrome is a well described but often forgotten condition. No randomised controlled trials of treatment have been published, although there are guidelines that use best available evidence for managing … Refeeding syndrome is a well described but often forgotten condition. No randomised controlled trials of treatment have been published, although there are guidelines that use best available evidence for managing the condition. In 2006 a guideline was published by the National Institute for Health and Clinical Excellence (NICE) in England and Wales. Yet because clinicians are often not aware of the problem, refeeding syndrome still occurs.1 This review aims to raise awareness of refeeding syndrome and discuss prevention and treatment. The available literature mostly comprises weaker (level 3 and 4) evidence, including cohort studies, case series, and consensus expert opinion.2 Our article also draws attention to the NICE guidelines on nutritional support in adults, with particular reference to the new recommendations for best practice in refeeding syndrome.3 These recommendations differ in parts from—and we believe improve on—previous guidelines, such as those of the Parenteral and Enteral Nutrition Group of the British Dietetic Association (box 1).4 #### Box 1 Why use the NICE guidelines on refeeding syndrome? Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally5). These shifts result …

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A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients

2013-04-17

Daren K. Heyland , John Muscedere , Paul E. Wischmeyer +6 more

Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically … Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance.There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).

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

2016-01-14

Stephen A. McClave , Beth Taylor , Robert G. Martindale +7 more

A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition … A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest-quality care for all critically ill and injured patients. These A.S.P.E.N.-SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, 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 current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutrition status, and insufficient statistical power for analysis. This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009.1 Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every 3–5 years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint "harmonization process" with the Canadian Clinical Guidelines group. Once completed, each group operated separately in its interpretation of the studies and derivation of guideline recommendations.2 The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was reconducted for all sections of the manuscript. The target of these guidelines is intended to be the adult (≥18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations, but like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill—primarily, physicians, nurses, dietitians, and pharmacists. The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the 2 societies. Literature searches were then performed using keywords (critically ill, critical care, intensive care, nutrition, enteral, parenteral, tube feeding, and those related to assigned topics, such as pancreatitis, sepsis, etc) to evaluate the quality of evidence supporting a response to those questions, which were then used to derive a subsequent treatment recommendation. The literature search included MEDLINE, PubMed, Cochrane Database of Systemic Reviews, the National Guideline Clearinghouse, and an Internet search using the Google search engine for scholarly articles through an end date of December 31, 2013 (including ePub publications). While preference was given to RCTs, other forms of resource material were used to support the response, including nonrandomized cohort trials, prospective observational studies, and retrospective case series. Use of publications was limited to full-text articles available in English on adult humans. For all included RCTs, 2 readers completed data abstraction forms (DAFs) examining the data and assessing the quality of the research methodology to produce a shared evaluation achieved by consensus for each study (example of DAF provided in online supplemental material). DAFs were constructed only for RCTs. When the strongest available evidence was a published meta-analysis, the studies from the meta-analysis were used to determine the quality of the evidence and assessed by 2 evidence assessors. The data from included trials were entered into Review Manager 5.2 software to create forest plots aggregating the effect size for each intervention and outcome.3 The key forest plots supporting the recommendation are included throughout the text and in the online appendix. No new forest plots were created when a meta-analysis was evaluated. Since release of the 2009 A.S.P.E.N. and SCCM Clinical Guidelines, the concepts of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group have been adopted.456-7 A full description of the methodology has been previously published.4 The data from the Review Manager analysis were uploaded to GRADEPro software,8 where the body of evidence for a given intervention and outcome was evaluated for overall quality. One analyst created each GRADE table that was then independently confirmed by a second analyst. The GRADE tables are provided in the online appendix. Due to the inordinately large number of RCTs evaluated, observational studies were critically reviewed but not utilized to construct the GRADE tables. However, in the few cases where observational studies were the only available evidence in a population, their quality of evidence was reviewed using GRADE (Table 1). When no RCT or observational study was available to answer a question directly, consensus of the author group on the best clinical practice approach was used, and the recommendation was designated "based on expert consensus." A recommendation for clinical practice was based on both the best available evidence and the risks and benefits to patients. While small author teams developed each recommendation and provided the supporting rationale, a full discussion by the entire author group followed, and every committee member was polled anonymously for his or her agreement with the recommendation. Achievement of consensus was arbitrarily set at 70% agreement of authors with a particular recommendation. Only 1 recommendation (H3a) did not meet this level of agreement, with a final consensus of 64%. All other consensus-based recommendations reached a level of agreement of 80% or higher. As with all A.S.P.E.N. and SCCM clinical guidelines, this manuscript was subjected to rigorous peer review by clinical content experts from all the practice disciplines that would use the guidelines, both internal and external to the organizations. A summary of the guidelines is presented in the online appendix. A nutrition bundle based on the top guidelines (as voted on by the committee) for the bedside practitioner is presented in Table 2. All authors completed both an A.S.P.E.N. and SCCM conflict-of-interest form for copyright assignment and financial disclosure. There was no input or funding from industry, nor were any industry representatives present at any of the committee meetings. Nutrition therapy refers specifically to the provision of either enteral nutrition (EN) by enteral access device and/or parenteral nutrition (PN) by central venous access. Standard therapy (STD) refers to provision of intravenous (IV) fluids, no EN or PN, and advancement to oral diet as tolerated. The significance of nutrition in the hospital setting (especially the ICU) cannot be overstated. Critical illness is typically associated with a catabolic stress state in which patients demonstrate a systemic inflammatory response coupled with complications of increased infectious morbidity, multiple-organ dysfunction, prolonged hospitalization, and disproportionate mortality. Over the past 3 decades, exponential advances have been made in the understanding of the molecular and biological effects of nutrients in maintaining homeostasis in the critically ill population. Traditionally, nutrition support in the critically ill population was regarded as adjunctive care designed to provide exogenous fuels to preserve lean body mass and support the patient throughout the stress response. Recently, this strategy has evolved to represent nutrition therapy, in which the feeding is thought to help attenuate the metabolic response to stress, prevent oxidative cellular injury, and favorably modulate immune responses. Improvement in the clinical course of critical illness may be achieved by early EN, appropriate macro- and micronutrient delivery, and meticulous glycemic control. Delivering early nutrition support therapy, primarily by the enteral route, is seen as a proactive therapeutic strategy that may reduce disease severity, diminish complications, decrease LOS in the ICU, and favorably impact patient outcomes. A1. Based on expert consensus, we suggest a determination of nutrition risk (eg, nutritional risk screening [NRS 2002], NUTRIC score) be performed on all patients admitted to the ICU for whom volitional intake is anticipated to be insufficient. High nutrition risk identifies those patients most likely to benefit from early EN therapy. Rationale: Poor outcomes have been associated with inflammation generated by critical illness that leads to deterioration of nutrition status and malnutrition.9 However, malnutrition in the critically ill has always been difficult to define. An international consensus group modified definitions to recognize the impact of inflammation. Objective measures of baseline nutrition status have been described by A.S.P.E.N. and the Academy of Nutrition and Dietetics.10,11 However, nutrition risk is easily defined and more readily determined by evaluation of baseline nutrition status and assessment of disease severity. All hospitalized patients are required to undergo an initial nutrition screen within 48 hours of admission. However, patients at higher nutrition risk in an ICU setting require a full nutrition assessment. Many screening and assessment tools are used to evaluate nutrition status, such as the Mini Nutritional Assessment, the Malnutrition Universal Screening Tool, the Short Nutritional Assessment Questionnaire, the Malnutrition Screening Tool, and the Subjective Global Assessment.12 However, only the NRS 2002 and the NUTRIC score determine both nutrition status and disease severity. Although both scoring systems were based on retrospective analysis, they have been used to define nutrition risk in RCTs in critically ill patients.131415-16 Patients at "risk" are defined by an NRS 2002 >3 and those at "high risk" with a score ≥5 or a NUTRIC score ≥5 (if interleukin-6 is not included, otherwise >6).1314151617-18 Interleukin-6 is rarely available as a component for the NUTRIC score; therefore, Heyland et al have shown that a NUTRIC score ≥5 still indicates high nutrition risk.19 Two prospective nonrandomized studies show that patients at high nutrition risk are more likely to benefit from early EN with improved outcome (reduced nosocomial infection, total complications, and mortality) than patients at low nutrition risk.13,18 While widespread use and supportive evidence are somewhat lacking to date, improvement in these scoring systems may increase their applicability in the future by providing guidance as to the role of EN and PN in the ICU. A2. Based on expert consensus, we suggest that nutrition assessment include an evaluation of comorbid conditions, function of the gastrointestinal (GI) tract, and risk of aspiration. We suggest not using traditional nutrition indicators or surrogate markers, as they are not validated in critical care. Rationale: In the critical care setting, the traditional serum 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.20 Anthropometrics are not reliable in assessment of nutrition status or adequacy of nutrition therapy.21 Individual levels of calcitonin, C-reactive protein (CRP), interleukin-1, tumor necrosis factor (TNF), interleukin-6, and citrulline are still investigational and should not be used as surrogate markers. Ultrasound is emerging as a tool to expediently measure muscle mass and determine changes in muscle tissue at bedside in the ICU, given its ease of use and availability.22,23 A computed tomography (CT) scan provides a precise quantification of skeletal muscle and adipose tissue depots; however, it is quite costly unless a scan taken for other purposes is used to determine body composition.24,25 Both may be valuable future tools to incorporate into nutrition assessment; however, validation and reliability studies in ICU patients are still pending. Assessment of muscle function is still in its infancy. Its measurement, reproducibility, and applicability are still being validated for use in critically ill patients and may be of value in the future. A3a. We suggest that indirect calorimetry (IC) be used to determine energy requirements, when available and in the absence of variables that affect the accuracy of measurement. [Quality of Evidence: Very Low] A3b. Based on expert consensus, in the absence of IC, we suggest that a published predictive equation or a simplistic weight-based equation (25–30 kcal/kg/d) be used to determine energy requirements. (See section Q for obesity recommendations.) Rationale: Clinicians should determine energy requirements to establish the goals of nutrition therapy. Energy requirements may be calculated through simplistic formulas (25–30 kcal/kg/d), published predictive equations, or IC. The applicability of IC may be limited at most institutions by availability and cost. Variables in the ICU that affect the timing and accuracy of IC measurements include the presence of air leaks or chest tubes, supplemental oxygen (eg, nasal cannula, bilevel positive airway pressure), ventilator settings (fractional inspiratory oxygen and positive end-expiratory pressure), continuous renal replacement therapy (CRRT), anesthesia, physical therapy, and excessive movement.26 More than 200 predictive equations have been published in the literature, with accuracy rates ranging from 40%–75% when compared with IC, and no single equation emerges as being more accurate in an ICU.2728293031-32 Predictive equations are less accurate in obese and underweight patients.333435-36 Equations derived from testing hospital patients (Penn State, Ireton-Jones, Swinamer) are no more accurate than equations derived from testing normal volunteers (Harris-Benedict, Mifflin St Jeor).37 The poor accuracy of predictive equations is related to many nonstatic variables affecting energy expenditure in the critically ill patient, such as weight, medications, treatments, and body temperature. The only advantage of using weight-based equations over other predictive equations is simplicity. However, in critically ill patients following aggressive volume resuscitation or in the presence of edema or anasarca, clinicians should use dry or usual body weight in these equations. Additional energy provided by dextrose-containing fluids and lipid-based medications such as propofol should be accounted for when deriving nutrition therapy regimens to meet target energy goals. Achieving energy balance as guided by IC measurements compared with predictive equations may lead to more appropriate nutrition intake. While 2 RCTs38,39 that met our inclusion criteria (with data from 161 patients) showed that higher mean intake of energy and protein was provided in IC-directed study patients compared with controls whose nutrition therapy was directed by predictive equations, issues with study design prevent a stronger recommendation for use of IC. In a study of burn patients, use of IC-directed nutrition therapy helped provide the minimal effective intake, avoiding the excesses of overfeeding seen in controls whose therapy was directed by the Curreri formula. Complications between groups (diarrhea and hyperglycemia) were no different, but traditional outcome parameters were not evaluated.38 A second study in general ICU patients used both EN and PN to meet target energy goals determined by IC measurement or a weight-based predictive equation (25 kcal/kg/d).39 While the IC-directed energy goal was no different from the value obtained by predictive equation (1976 ± 468 vs 1838 ± 468 kcal/d, respectively; P = .60), only study patients were monitored vigilantly by an ICU dietitian, while controls were managed by standard of care (less frequent ICU dietitian monitoring), which led to significantly more energy and protein per day in the study patients. The trend toward reduced mortality in study patients compared with controls (risk ratio [RR] = 0.63; 95% confidence interval [95% CI], 0.39–1.02; P = .06) is difficult to reconcile in light of their increased morbidity with regard to ICU LOS (17.2 ± 14.6 vs 11.7 ± 8.4 days; P = .04) and duration of mechanical ventilation (16.1 ± 14.7 vs 10.5 ± 8.3 days; P = .03).38,39 Whether measured by IC or estimated by predictive equations, energy expenditure should be reevaluated more than once per week, and strategies to optimize energy and protein intake should be used.39,40 A4. Based on expert consensus, we suggest an ongoing evaluation of adequacy of protein provision be performed. 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 thus are not easily met by provision of routine enteral formulations (which have a high nonprotein calorie:nitrogen ratio [NPC:N]). Patients with suboptimal EN due to frequent interruptions may benefit from protein supplementation. The decision to add protein modules should be based on an ongoing assessment of adequacy of protein intake. Weight-based equations (eg, 1.2–2.0 g/kg/d) may be used to monitor adequacy of protein provision by comparing the amount of protein delivered with that prescribed, especially when nitrogen balance studies are not available to assess needs (see section C4).41,42 Serum protein markers (albumin, prealbumin, transferrin, CRP) are not validated for determining adequacy of protein provision and should not be used in the critical care setting in this manner.20,43 B1. We recommend that nutrition support therapy in the form of early EN be initiated within 24–48 hours in the critically ill patient who is unable to maintain volitional intake. [Quality of Evidence: Very Low] 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 (eg, cholecystokinin, gastrin, bombesin, and bile salts). EN maintains structural integrity by maintaining villous height and supporting the mass of secretory IgA-producing immunocytes (B cells and plasma cells) that compose the gut-associated lymphoid tissue (GALT) and in turn contribute to mucosal-associated lymphoid tissue at distant sites such as the lungs, liver, and kidneys.4445-46 Adverse change in gut permeability from loss of functional integrity is a dynamic phenomenon that 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 multiple-organ dysfunction syndrome.45,46 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 LOS.47 The specific reasons for providing EN are to maintain gut integrity, modulate stress and the systemic immune response, and attenuate disease severity.44,47,48 Additional end points of EN therapy may 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. Three previous meta-analyses aggregated data from RCTs comparing early versus delayed EN. One meta-analysis of 8 trials by Heyland et al showed a trend toward reduced mortality (RR = 0.52; 95% CI, 0.25–1.08; P = .08)49 when EN was started within 48 hours, compared with delayed initiation of EN started after that point. A second meta-analysis of 12 trials by Marik et al showed significant reductions in infectious morbidity (RR = 0.45; 95% CI, 0.30–0.66; P = .00006) and hospital LOS (mean, 2.2 days; 95% CI, 0.81–3.63 days; P = .001) when early EN was started on average within 36 hours of ICU admission.50 A third meta-analysis of 6 trials by Doig et al showed a significant reduction in pneumonia (odds ratio [OR] = 0.31; 95% CI, 0.12–0.78; P = .01) and mortality (OR = 0.34; 95% CI, 0.14–0.85; P = .02) but no difference in multiple-organ failure (MOF) when early EN was started within 24 hours of admission to the ICU, compared with EN started after that point.51 Of an updated meta-analysis of 21 RCTs that met our inclusion criteria comparing the provision of early EN versus delayed EN, all reported on mortality (Figure 1), with 13 reporting on infection (Figure 2). Provision of early EN was associated with a significant reduction in mortality (RR = 0.70; 95% CI, 0.49–1.00; P = .05) and infectious morbidity (RR = 0.74; 95% CI, 0.58–0.93; P = .01), compared with withholding early EN (delayed EN or STD). Early enteral nutrition (EN) vs delayed EN, mortality. Early enteral nutrition (EN) vs delayed EN, infectious complications. B2. We suggest the use of EN over PN in critically ill patients who require nutrition support therapy. [Quality of Evidence: Low to Very Low] Rationale: In the majority of critically ill patients, it is practical and safe to use EN instead of PN. The beneficial effects of EN compared with PN are well documented in numerous RCTs involving a variety of patient populations in critical illness, including trauma, burns, head injury, major surgery, and acute pancreatitis.47,49,5253-54 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; specifically, abdominal abscess in trauma patients) and ICU LOS. Six previous meta-analyses comparing EN with PN showed significant reductions in infectious morbidity with use of EN.49,55565758-59 Noninfective complications (risk difference = 4.9; 95% CI, 0.3–9.5; P = .04) and reduced hospital LOS (weighted mean difference [WMD] = 1.20 days; 95% CI, 0.38–2.03; P = .004) were seen with use of EN compared with PN in one of the meta-analyses by Peter et al.57 Five of the meta-analyses showed no difference in mortality between the 2 routes of nutrition support therapy.49,55565758-59 One meta-analysis by Simpson and Doig 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 with EN.59 In 12 studies53,58,606162636465666768-69 representing 618 patients that met our inclusion criteria, 9 reported on infection (Figure 3), which was shown to be significantly less with EN than PN (RR = 0.56; 95% CI, 0.39–0.79; P < .00001). ICU LOS also was shorter with EN compared with PN by nearly 1 full day (WMD = −0.82 days; 95% CI, −1.29 to −0.34; P = .0007). Hospital LOS and mortality were not significantly different. These differences in outcome from the separate routes of feeding largely reflect findings from older studies and may diminish in the future with improvements in glycemic control, protocolized medical management, and new lipid emulsions. Enteral nutrition (EN) vs parenteral nutrition (PN), infectious complications. B3. Based on expert consensus, we suggest that, in the majority of MICU and SICU patient populations, while GI contractility factors should be evaluated when initiating EN, overt signs of contractility should not be required prior to initiation of EN. 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 EN. GI dysfunction in the ICU setting occurs in 30%–70% of patients, depending on the diagnosis, premorbid condition, ventilation mode, medications, and metabolic state.70 Proposed mechanisms of ICU and postoperative GI dysfunction are related to mucosal barrier disruption, altered motility, atrophy of the mucosa, and reduced mass of GALT. GI intolerance has been variably defined (eg, absence or abnormal bowel sounds, vomiting, bowel dilatation, diarrhea, GI bleeding, high gastric residual volumes [GRVs]) and appears to occur in up to 50% of patients on mechanical ventilation. Bowel sounds are indicative only of contractility and do not necessarily relate to mucosal integrity, barrier function, or absorptive capacity. The argument for initiating EN regardless of the extent of audible bowel sounds is based on studies (most of which involve critically ill surgical patients) reporting the feasibility and safety of EN within the initial 36–48 hours of admission to the ICU. Nonetheless, reduced or absent bowel sounds may reflect greater disease severity and worsened prognosis. Patients with normal bowel sounds have been shown to have lower ICU mortality than those with hypoactive or absent bowel sounds (11.3% vs 22.6% vs 36.0%, respectively).71 ICU LOS has been shown to increase with greater number of symptoms of GI intolerance (2.9 days when asymptomatic vs up to 16.8 days with 4 symptoms of intolerance).72 Not surprising, success of EN delivery is reduced with a greater number of symptoms of GI intolerance. A greater number of signs of intolerance may warrant increased vigilance as EN is started and may necessitate further clinical evaluation. B4a. We recommend that the level of infusion be diverted lower in the GI tract in those critically ill patients at high risk for aspiration (see section D4) or those who have shown intolerance to gastric EN. [Quality of Evidence: Moderate to High] B4b. Based on expert consensus we suggest that, in most critically ill patients, it is acceptable to initiate EN in the stomach. Rationale: Initiating EN therapy in the stomach is technically easier and may decrease the time to initiation of EN. The choice of level of infusion within the GI tract (ie, whether the tip of the feeding tube is in the stomach, different segments of the duodenum [D1, D2, D3, or D4], or the jejunum) may be determined by patient selection within ICU practitioners' institutional framework (ease and feasibility of placing small bowel enteral access devices, institutional policies, and protocols). In the largest multicenter RCT to compare gastric versus small bowel EN in critically ill patients, Davies et al found no difference in clinical outcomes between groups, including LOS, mortality, nutrient delivery, and incidence of pneumonia.73 Aggregating the data from the RCTs that met our inclusion criteria, 6 trials reported on improved nutrient delivery with small bowel feedings (WMD = 11.06%; 95% CI, 5.82–16.30%; P < .00001) (Figure 4),7374757677-78 and 12 trials demonstrated a reduced risk of pneumonia compared with gastric EN (RR = 0.75; 95% CI, 0.60–0.93; P = .01) (Figure 5).7374757677787980818283-84 Although small bowel EN decreases the risk of pneumonia, there is no difference in mortality or LOS between small bowel and gastric EN. Therefore, if timely obtainment of small bowel enteral access device is not feasible, early EN via the gastric route may provide more benefit than delaying feeding initiation while awaiting small bowel access.73 Small bowel vs gastric feedings, nutrition efficiency. Gastric vs small bowel feedings, pneumonia. B5. Based on expert consensus, we suggest that in the setting of hemodynamic compromise or instability, EN should be withheld until the patient is fully resuscitated and/or stable. Initiation/reinitiation of EN may be considered with caution in patients undergoing withdrawal of vasopressor support. 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 injuries involving the intestinal microcirculation. Ischemic bowel is a very rare complication associated with EN.85 In a retrospective review of patients

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Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial

2012-02-05

Todd W. Rice , Arthur P. Wheeler , Bruce Thompson +6 more

Context-The amount of enteral nutrition patients with acute lung injury need is unknown.Objective-To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with … Context-The amount of enteral nutrition patients with acute lung injury need is unknown.Objective-To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding. Design, Setting, and Participants-The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011.Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.Interventions-Participants were randomized to receive either trophic or full enteral feeding for the first 6 days.After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol.Main Outcome Measures-Ventilator-free days to study day 28.Results-Baseline characteristics were similar between the trophic-feeding (n=508) and fullfeeding (n=492) groups.The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P<.001).Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P=.89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P=77) compared with full feeding.There were no differences in infectious complications between the

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Early versus Late Parenteral Nutrition in Critically Ill Adults

2011-06-30

Michaël P. Casaer , Dieter Mesotten , Greet Hermans +7 more

Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone.In this randomized, multicenter trial, … Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone.In this randomized, multicenter trial, we compared early initiation of parenteral nutrition (European guidelines) with late initiation (American and Canadian guidelines) in adults in the intensive care unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients, parenteral nutrition was initiated within 48 hours after ICU admission (early-initiation group), whereas in 2328 patients, parenteral nutrition was not initiated before day 8 (late-initiation group). A protocol for the early initiation of enteral nutrition was applied to both groups, and insulin was infused to achieve normoglycemia.Patients in the late-initiation group had a relative increase of 6.3% in the likelihood of being discharged alive earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13; P=0.04), without evidence of decreased functional status at hospital discharge. Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups. Patients in the late-initiation group, as compared with the early-initiation group, had fewer ICU infections (22.8% vs. 26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late-initiation group had a relative reduction of 9.7% in the proportion of patients requiring more than 2 days of mechanical ventilation (P=0.006), a median reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a mean reduction in health care costs of €1,110 (about $1,600) (P=0.04).Late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation. (Funded by the Methusalem program of the Flemish government and others; EPaNIC ClinicalTrials.gov number, NCT00512122.).

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The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study

2009-07-01

Cathy Alberda , Leah Gramlich , N. F. Jones +4 more

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Long-Term Total Parenteral Nutrition with Growth, Development, and Positive Nitrogen Balance

2023-12-12

Stanley J. Dudrick , Douglas W. Wilmore , Harry M. Vars +1 more

This chapter is an experimental and follow-up clinical study showing that normal life could be sustained using parenteral means only. The experimental element involved six beagle puppies who were paired … This chapter is an experimental and follow-up clinical study showing that normal life could be sustained using parenteral means only. The experimental element involved six beagle puppies who were paired after weaning at eight weeks of age with control littermates. Then, at 12 weeks a vinyl catheter was inserted into an external jugular vein and threaded to the superior vena cava. The end was tunnelled to be brought out on the back between the scapulae and the puppies' attached to a harness in a 'metabolic' cage. Stanley Dudrick was a surgical resident working at the University of Pennsylvania in 1967 with his mentor Jonathan Rhoads. He became the first president and founder of the American Society for Parenteral and Enteral Nutrition. Jonathan Rhoads, an adult cancer surgeon, had an equally prestigious career editing the Annals of Surgery and writing the Rhoads' Textbook of Surgery.

Treating Patients with Severe Sepsis

1999-01-21

Arthur P. Wheeler , Gordon R. Bernard

Sepsis is an infection-induced syndrome defined as the presence of two or more of the following features of systemic inflammation: fever or hypothermia, leukocytosis or leukopenia, tachycardia, and tachypnea or … Sepsis is an infection-induced syndrome defined as the presence of two or more of the following features of systemic inflammation: fever or hypothermia, leukocytosis or leukopenia, tachycardia, and tachypnea or a supranormal minute ventilation.1 When an organ system begins to fail because of sepsis, the sepsis is considered severe. Each year, sepsis develops in more than 500,000 patients in the United States, and only 55 to 65 percent survive.2,3 Fortunately, the death rates in some subgroups of patients with sepsis-induced organ failure have decreased, even though there is no specific therapy for sepsis.3,4 The reduced mortality may be . . .

Parenteral nutrition before gastrointestinal surgery.

1982-03-20

Tweedle De

Perioperative Total Parenteral Nutrition in Surgical Patients

1992-01-23

M. León‐Sanz

ESPEN Guidelines on Enteral Nutrition: Intensive care

2006-04-01

K. Georg Kreymann , Marc Moritz Berger , Nicolaas E.P. Deutz +7 more

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

2017-02-06

Annika Reintam Blaser , Joel Starkopf , Waleed Alhazzani +7 more

To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as … To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

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Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients

2002-01-01

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

2009-04-27

Stephen A. McClave , Robert G. Martindale , Vincent W. Vanek +6 more

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 … 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. These guidelines may be subject to periodic review and revision based on new peer-reviewed critical care nutrition literature and practice. 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. 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. 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. 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. 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 B1. If early EN is not feasible or available the first 7 days following admission to the ICU, no nutrition support therapy (ie, STD therapy) should be provided. (Grade: C) In the patient who was previously healthy prior to critical illness with no evidence of protein-calorie malnutrition, use of PN should be reserved and initiated only after the first 7 days of hospitalization (when EN is not available). (Grade: E) Rationale. These 2 recommendations are the most controversial in these guidelines, are influenced primarily by 2 meta-analyses, and should be interpreted very carefully in application to patient care.24,92 Both meta-analyses compared use of PN with STD therapy (where no nutrition support therapy was provided). In critically ill patients in the absence of pre-existing malnutrition (when EN is not available), Braunschweig et al aggregated 7 studies93-99 and showed that use of STD therapy was associated with significantly reduced infectious morbidity (RR = 0.77; 95% CI 0.65-0.91; P <.05) and a trend toward reduced overall complications (RR = 0.87; 95% CI 0.74-1.03; P not provided) compared to use of PN.24 In the same circumstances (critically ill, no EN available, and no evidence of malnutrition), Heyland et al92 aggregated 4 studies96,97,100,101 and showed a significant increase in mortality with use of PN (RR = 0.1.78; 95% CI 1.11-2.85; P < .05) and a trend toward greater rate of complications (RR = 2.40; 95% CI 0.88-6.58; P not provided), when compared to STD therapy. See Table 6 . 93-129 With increased duration of severe illness, priorities between STD therapy and PN become reversed. Sandstrom et al first showed that after the first 14 days of hospitalization had elapsed, continuing to provide no nutrition therapy was associated with significantly greater mortality (21% vs 2%, P < .05) and longer hospital length of stay (36.3 days vs 23.4 days, P < .05), when compared respectively to use of PN.96 The authors of both metaanalyses speculated as to the appropriate length of time before initiating PN in a patient on STD therapy who has not begun to eat spontaneously (Braunschweig recommending 7-10 days, Heyland recommending 14 days).24,92 Conflic ting data were reported in a Chinese study of patients with severe acute pancreatitis. In this study, a significant step-wise improvement was seen in each clinical outcome parameter (hospital length of stay, pancreatic infection, overall complications, and mortality) when comparing patients randomized to STD therapy vs PN vs PN with parenteral glutamine, respectively.121 Because of the discrepancy, we attempted to contact the authors of this latter study to get validation of results but were unsuccessful. The final recommendation was based on the overall negative treatment effect of PN over the first week of hospitalization seen in the 2 metaanalyses.24,92 Although the literature cited recommends withholding PN for 10-14 days, the Guidelines Committee expressed concern that continuing to provide STD therapy (no nutrition support therapy) beyond 7 days would lead to deterioration of nutrition status and an adverse effect on clinical outcome. B2. If there is evidence of protein-calorie malnutrition on admission and EN is not feasible, it is appropriate to initiate PN as soon as possible following admission and adequate resuscitation. (Grade: C) Rationale. In the situation where EN is not available and evidence of protein-calorie malnutrition is present (usually defined by recent weight loss of >10%-15% or actual body weight <90% of ideal body weight), initial priorities are reversed and use of PN has a more favorable outcome than STD therapy. See Table 6 . 93-129 In the Heyland meta-analysis, use of PN in malnourished ICU patients was associated with significantly fewer overall complications (RR = 0.52; 95% CI 0.30-0.91; P < .05) than STD therapy.92 In the Braunschweig meta-analysis, STD therapy in malnourished ICU patients was associated with significantly higher risk for mortality (RR = 3.0; 95% CI 1.09-8.56; P < .05) and a trend toward higher rate of infection (RR = 1.17; 95% CI 0.88-1.56; P not provided) compared to use of PN.24 For these patients, when EN is not available, there should be little delay in initiating PN after admission to the ICU. B3. If a patient is expected to undergo major upper GI surgery and EN is not feasible, PN should be provided under very specific conditions: If the patient is malnourished, PN should be initiated 5-7 days preoperatively and continued into the postoperative period. (Grade: B) PN should not be initiated in the immediate postoperative period but should be delayed for 5-7 days (should EN continue not to be feasible). (Grade: B) PN therapy provided for a duration of <5-7 days would be expected to have no outcome effect and may result in increased risk to the patient. Thus, PN should be initiated only if the duration of therapy is anticipated to 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 seven95,98,102,103,107,110,111 out of 14 studies94,100,104,106,108,109,112 provided PN for ≥7 days.130 As a result, only 1 study showed a treatment effect95 and the overall meta-analysis showed no statistically significant benefit from PN.130 In contrast, a later meta-analysis by Klein et al131 aggregated the data from 13 studies,95,98,103,105,111,113-120 all of which provided PN for ≥7 days.131 Six of the studies showed significant beneficial treatment effects from use of PN,95,103,105,111,115,120 with the pooled data from the overall meta-analysis showing a significant 10% decrease in infectious morbidity compared to STD therapy.131 See Table 6 . 93-129 It is imperative to be aware that the beneficial effect of PN is lost if given only postoperatively. Aggregation of data from 9 studies that evaluated routine postoperative PN93,94,96,99-101,104,109,122 showed a significant 10% increase in complications compared to STD therapy.131 Because of the adverse outcome effect from PN initiated in the immediate postoperative period, Klein et al recommended delaying PN for 5-10 days following surgery if EN continues not to be feasible.131 C1. The target goal of EN (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy. (Grade: C) Energy requirements may be calculated by predictive equations or measured by indirect calorimetry. Predictive equations should be used with caution, as they provide a less accurate measure of energy requirements than indirect calorimetry in the individual patient. In the obese patient, the predictive equations are even more problematic without availability of indirect calorimetry. (Grade: E) Rationale. Clinicians should clearly identify the goal of EN, as determined by energy requirements. Over 200 predictive equations (including Harris-Benedict, Scholfield, Ireton-Jones, etc) have been published in the literature.132 Energy requirements may be calculated either through simplistic formulas (25-30 kcal/kg/d), published predictive equations, or the use of indirect calorimetry. Calories provided via infusion of propofol should be considered when calculating the nutrition regimen. While it is often difficult to provide 100% of goal calories by the enteral route, studies in which a protocol was used to increase delivery of EN have shown that delivering a volume of EN where the level of calories and protein provided is closer to goal improves outcome.133,134 This recommendation is supported by two level II studies in which those patients who by protocol randomization received a greater volume of EN experienced significantly fewer complications and less infectious morbidity,23 as well as shorter hospital lengths of stay, and a trend toward lower mortality135 than those patients receiving lower volume. C2. Efforts to provide >50%-65% of goal calories should be made in order to achieve the clinical benefit of EN over the first week of hospitalization. (Grade: C) Rationale. The impact of early EN on patient outcome appears to be a dose-dependent effect. “Trickle” or trophic feeds (usually defined as 10-30 mL/h) may be sufficient to prevent mucosal atrophy but may be insufficient to achieve the usual endpoints desired from EN therapy. Studies suggest that >50%-65% of goal calories may be required to prevent increases in intestinal permeability in burn and bone-marrow transplant patients, to promote faster return of cognitive function in head injury patients, and to improve outcome from immune-modulating enteral formulations in critically ill patients.5,23,133,136 This recommendation is supported by one level II23 and one level III study136 where increases in the percent goal calories infused from a range of 37%-40% up to 59%-64% improved clinical outcome. C3. If unable to meet energy requirements (100% of target goal calories) after 7-10 days by the enteral route alone, consider initiating supplemental PN. (Grade: E) Initiating supplemental PN prior to this 7-10 day period in the patient already receiving EN does not improve outcome and may be detrimental to the patient. (Grade: C) Rationale. Early on, EN is directed toward maintaining gut integrity, reducing oxidative stress, and modulating systemic immunity. In patients already receiving some volume of EN, use of supplemental PN over the first 7-10 days adds cost137,138 and appears to provide no additional benefit.42,137-140 In 1 small study in burn patients, EN supplemented with PN was associated with a significant increase in mortality (63% vs 26%, P < .05) when compared respectively to hypocaloric EN alone.138 See Table 7 . 42,137-140 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

ESPEN guideline on clinical nutrition in the intensive care unit

2018-09-29

Pierre Singer , Annika Reintam Blaser , Mette M. Berger +7 more

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Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation

2018-10-23

Vinícius Fernandes Cruzat , Marcelo Macedo Rogero , Kevin N. Keane +2 more

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. … Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities, and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver, and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g., ill/critically ill, post-trauma, sepsis, exhausted athletes), it is currently difficult to determine whether glutamine supplementation (oral/enteral or parenteral) should be recommended based on the amino acid plasma/bloodstream concentration (also known as glutaminemia). Although the beneficial immune-based effects of glutamine supplementation are already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review of how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism and action, and important issues related to the effects of glutamine supplementation in catabolic situations.

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Nutrient Requirements of Dogs and Cats

2006-05-31

Board on Agriculture , Subcommittee on Dog , Cat Nutrition +1 more

Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability

1989-03-01

Ismael J. Hidalgo , Thomas J. Raub , Ronald T. Borchardt

A Multicompartmental Dynamic Computer-controlled Model Simulating the Stomach and Small Intestine

1995-03-01

Mans Minekus , Phillipe Marteau , R. Havenaar +1 more

A multicompartmental in vitro model has been described, which simulates the dynamic events occurring within the lumen of the gastrointestinal tract of man and monogastric animals. The accuracy of the … A multicompartmental in vitro model has been described, which simulates the dynamic events occurring within the lumen of the gastrointestinal tract of man and monogastric animals. The accuracy of the model for reproducing in vivo data on gastrointestinal transit, pH, bile salt concentrations and the absorption of glucose was tested. The in vivo conditions simulated in the model were based on studies in healthy human volunteers. Mathematical modelling of gastric and ileal delivery with power exponential equations was used for the computer control of meal transit. The model appeared to reproduce accurately the pre-set data on meal transit, pH and bile salt concentrations in the different gastrointestinal compartments. Glucose absorption from the small intestine was almost complete. This model reproduces very closely the dynamic conditions based on the in vivo situation in monogastric animals and man. Therefore, the model can be an important tool in studying the fate of ingested components (for example, food, microorganisms and medicines) during gastrointestinal transit and, consequently, may contribute to the replacement of studies using laboratory animals.

Percutaneous endoscopic gastrostomy

1987-07-01

David E. Larson , Duane D. Burton , Kenneth W. Schroeder +1 more

Clinical Nutrition and Gastroenterology

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