Nutrition Support in Clinical Practice: Review of Published Data and

Am J Clin Nuir 1997:66:683-706. Printed in USA. 0 1997 American Society for Clinical Nutrition 683

Nutrition Support in Clinical Practice: Review of Published Data andRecommendations for Future Research Directions

Summary of a Conference Sponsored by the National Institutes of Health, American Society for

Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition

SAMUEL KLEIN, MD; JohN KINNEY, MD; KHURSHEED JEEJEEBHOY, MB, BS, PiiD; DA\ID ALPERS, MD; MARK HELLERSTEIN, MD, Th-ID;

MICHAEL MURRAY, MD, Pi�iD; PATRICK TWO�IEY, MD; AND 0THERS*

ABSTRAC’fl In the last 30 years, marked advances in enteralfeeding techniques, venous access, and enteral and parenteralnutrient formulations have made it possible to provide nutritionsupport to almost all patients. Despite the abundant medical lit-

erature and widespread use of nutritional therapy, many areas of

nutrition support remain controversial. Therefore, the leadershipat the National Institutes of Health, The American Society forParenteral and Enteral Nutrition, and The American Society for

Clinical Nutrition convened an advisory committee to perform a

critical review of the current medical literature evaluating theclinical use of nutrition support; the goal was to assess our cur-rent body of knowledge and to identify the issues that deserve

further investigation. The panel was divided into five groups to

evaluate the following areas: nutrition assessment, nutrition sup-port in patients with gastrointestinal diseases, nutrition supportin wasting diseases, nutrition support in critically ill patients, andperioperative nutrition support. The findings from each group

are summarized in this report.This document is not meant to establish practice guidelines for

nutrition support. The use of nutritional therapy requires a care-ful integration of data from pertinent clinical trials, clinical ex-

pertise in the illness or injury being treated, clinical expertise innutritional therapy, and input from the patient and his/her family.

(Journal ofParenteral and Enteral Nutrition 21:133-156, 1997)

In the past 30 years, marked advances in enteral feeding

techniques, venous access, and enteral and parenteral nutri-

ent formulations have made it possible to provide nutrition

support to almost all patients. Information regarding the useof nutrition support has increased dramatically. In the past

20 years, there has been a 10-fold increase in the annual rate

ofenteral and parenteral nutrition-related publications, from

50 per year in the early 1970s to 525 per year in the early

1990s. The sophistication of nutrition technology has made

clinical nutrition agrowing medical subspecialty with its ownsocieties and journals. Despite the abundant medical litera-

ture and widespread use of nutritional therapy, many areas

ofnutrition support remain controversial. Therefore, the lead-

ership at the National Institutes ofHealth, The American So-ciety for Parenteral and Enteral Nutrition, and The Amen-can Society for Clinical Nutrition concurred that a critical

review of the current medical literature evaluating the cmi-

cal use ofnutrition support was warranted to assess our cur-rent body of knowledge and to identify the issues that de-

serve further investigation. To this end, an advisory committee

representing the three organizations was formed, and a panel

of experts were recruited to review the current published

*See appendix.

The opinions presented in this report are those of the authors and do not

necessarily represent the opinions of the National Institutes of Health,the American Society for Clinical Nutrition, or A.S.P.E.N.

Received for publication, April 14, 1997Accepted for publication, April 17, 1997Correspondence: Samuel Klein, MD, Washington tniversity School of Men-cine, 660 South Euclid Avenue, Box 8127, St. Louis, MO 63110-1093.

literature and make recommendations for future research

directions.

The panel was divided into five groups to evaluate the fol-

lowing areas: (1) nutrition assessment, (2) nutrition support

in patients with gastrointestinal diseases, (3) nutrition sup-

port in wasting diseases, (4) nutrition support in critically ill

patients, and (5) penoperative nutrition support. The find-

ings from each group are summarized in this report. Each

section represents a critical review of the available literature

and contains suggestions for future research. Whenever pos-

sible, prospective randomized clinical trials (PRCTh) were

evaluated because this is the most reliable method for evalu-

ating clinical efficacy of a treatment. However, other pub-

lished reports were also reviewed when appropriate PRCTs

were not available. Each conclusion was graded on the basis

of the strength of the supporting data, as follows: A = sup-

ported by PRCTs or meta-analyses of PRCTh; B = supported

by well-designed nonrandomized prospective, retrospective,

or case cohort controlled studies; and C = supported by un-

controlled published experiences, case reports, or expert

opinion.

This document is not meant to establish practice guide-

lines for nutrition support. The use of nutritional therapy re-

quires a careful integration of data from pertinent clinical

trials, clinical expertise in the illness or injury being treated,

clinical expertise in nutritional therapy, and sometimes in-

put from the patient and his/her family.

NUTRITION ASSESSMENT

The field of nutrition support is based on two closely re-

lated concepts: (1)nutrient depletion is associated with in-

creased morbidity and mortality, and (2) ifthis association is

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684 NUTRITION SUPPORT IN CLINICAL PRACTICE

causative, the prevention or correction of nutrient deple-

tion can minimize or eliminate malnutrition-related mor-bidity and mortality. This construct leads to three poten-tial goals of nutrition assessment:

1. To identify patients who have, or are at risk of de-

veloping, protein-energy malnutrition or specific nu-trient deficiencies.

2. To quantify a patient’s risk of developing malnutri-

tion-related medical complications.3. To monitor the adequacy of nutritional therapy.

This section concentrates on goal 2 because it was con-sidered by the subcommittee to be the most important.

At some point, the presence of protein-energy malnutri-tion or specific nutrient deficiencies increases morbid-ity and mortality. However, the ability to use nutrition

assessment to predict clinical outcome can be problem-

atic because the interaction between malnutrition and

other factors that influence outcome makes it difficultto isolate any putative contribution from malnutritionalone. For example, illness and injury can affect tissuemetabolism and accelerate loss of tissue function andmass. Inadequate protein and energy intake can also leadto alterations in intermediary metabolism, tissue func-tion, and body composition. Therefore, the presence of“malnutrition” can contribute to a poor clinical outcomeor may simply be associated with a poor outcome if thedisease itself affects markers of “nutritional status.”

The problem of malnutrition in hospitalized patientswas highlighted by several publications in the 1970s)�The high prevalence of malnutrition and the introduc-tion of modern enteral and parenteral feeding techniquesin the 1970s and 1980s stimulated the development of

several formal approaches for evaluating nutritional sta-

tus. All these approaches link nutrition assessment with

clinical outcome.

NUTRITIONAL ASSESSMENT TECHNIQUES

Body Composition Analyses

The body consists of35 components, which are organizedinto five levels of increasing complexity: atomic (eg, nitro-gen, potassium); molecular (eg, water, protein); cellular (eg,body cell mass, intracellular and extracellular fluid); tissue(eg, skeletal muscle, adipose tissue); and whole body (eg,weight, height). Although modern technology now allowsmeasurement of all major body components in vivo, these

methodologies are not readily available for clinical use. Fur-

thermore, no body composition measurement has beenshown to consistently predict clinical outcome.

Body Weightand Weight Loss

Body weight is a practical and simple measure of totalbody components. Weight can be compared with an “ideal”or “desirable” weight, or assessment of body mass index[weight (kg)/height(m)2� can be used to determine both un-dernutrition and overnutrition. However, measurement ofbody weight in sick patients is confounded by changes in

body water because ofdehydration, edema, and ascites. Fur-thermore, a person who starts at the upper end of the nor-mal range may be classified as “normal” despite consider-able changes in the measured value.

Unintentional weight loss greater than 10% within the pre-vious 6 months is a good prognosticator ofdllnical outcome.6

However, it can be difficult to determine true weight loss

because of errors in recall. Morgan et al7 found that 33% ofpatients with weight loss would be missed and 25% ofweight-stable patients would be diagnosed as having lost

weight when weight loss is based on patient recall. Further-more, small changes in body weight can be confounded bychanges in hydration status.

Anthropometry

Thceps and subscapular skinfold thicknesses provide an

index of body fat, and midarm muscle circumference pro-vides a measure of muscle mass. The most commonly usedstandards for triceps skinfold thickness and midarm musclecircumference are those reported by Jelliffe,8 which are basedon measurements of European military men and low-incomeAmerican women, and those reported by Frisancho,9 whichare based on measurements of white males and females par-ticipating in the 1971-1974 US Health and Nutrition Survey.The use of these standards to identify malnutrition in manypatients is problematic because of the restricted databaseand the potential confounding influence of age, hydrationstatus, and physical activity. Several studies have demon-strated that 20% to 30% ofhealthy control subjects would beconsidered malnourished on the basis ofthese standards’#{176}”and that there is poor correlation between Jellife’s and

Frisancho’s standards in classifying ts’ Furthermore,interpretation of the data may be limited by inter-rater van-ability’2 and the patient’s hydration status. Nevertheless,markedly abnormal values (below the 5th percentile) areoften associated with poor clinical outcome.

Creatinine-Height Index

The excretion of creatinine in urine provides an index oflean body ass’3 However, it is dependent upon an accurateand complete urine collection while the patient is consum-ing a meat-free diet, which can be difficult to achieve in somepatient care settings.

Serum Protein Concentrations

Albumin. Several studies have demonstrated that a lowserum albumin concentration correlates with an increasedincidence ofmedical complications.’4’6 Sick patients mayhave low levels of serum albumin for several reasons.’7Inflammatory disorders cause a decrease in albumin syn-thesis, an increase in albumin degradation, and an increasein albumin transcapifiary losses. Gastrointestinal and somecardiac diseases increase albumin losses through the gut,and renal diseases can cause albuminuria Wounds, burns,and peritonitis cause major losses from the injured sur-face. Because the exchange between intravascular and ex-travascular albumin is so large, even small variations inthe percentage of exchange can cause significant changesin plasma albumin levels. The normal rate of albumin ex-

change between intravascular and extravascular compart-ments is more than 10 times the rate of albumin synthesisor degradation. During serious illness, vascular permeabil-ity increases dramatically. Albumin losses from plasma to

the extravascular space were increased twofold in patientswith cancer cachexia and threefold in patients with septic

shock. Plasma albumin levels are usually not affected bynutritional intake and will not increase in stressed patientsuntil the inflammatory stress ts’8

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INTERSOCIETY COMMUNICATION 685

Serum albumin may not be a good measure of the ad-

equacy of nutrient intake. Although protein-energy mal-nutrition causes a decrease in the rate of albumin synthe-sis, this may have little impact on albumin levels because

of albumin’s long half-life and large pool size. Indeed,

plasma albumin concentration may actually increase dur-

ing short-term fasting because of contraction of intravas-cular water.’9 Even during chronic malnutrition, plasmaalbumin concentration is often nmintained because of acompensatory decrease in albumin degradation and a

transfer of extravascular albumin to the intravascular corn-

partment. Prolonged protein-energy restriction inducedexperimentally in human volunteers20 or observed clini-cally in patients with anorexia nervosa2’ causes marked

reductions in body weight but little change in plasma

albumin concentration. A protein-deficient diet with

adequate calories in elderly persons decreases lean bodymass and muscle function without a change in plasma al-

bumin concentration.22Prealbumin. Prealbumin is a transport protein for thy-

roid hormones and exists in the circulation as a retinol-binding-prealbumin complex. The turnover rate of thisprotein is rapid, with a half-life of 2 to 3 days. It is synthe-

sized by the liver and is catabolized partly in the kidneys.

Protein-energy malnutrition reduces the levels of

prealbumin, and refeeding (particularly with carbohydrate)

restores levels.23 However, prealbumin levels decrease

without malnutrition in infections24 and in response tocytokine25 and hormone infusion.2� Renal failure in-

creases,27 while liver failure may decrease, plasma con-

centrations.

Immune Competence

Immune incompetence, as measured by delayed cuta-neous hypersensitivity (DCH), has been shown to be as-

sociated with a poor clinical outcome. Although DCH isaffected by severe malnutrition, several diseases and drugsinfluence DCH, making it a poor measure of malnutrition

in sick patients. The following factors alter DCH in theabsence ofmalnutrition: (1) infections (viral, bacterial, and

granulomatous); (2) illnesses (uremia, cirrhosis, hepati-

tis, trauma, burns, and hemorrhage); (3) medications (cor-

ticosteroids, immunosuppressants, cimetidine, warfarin,and perhaps aspirin); and (4) general anesthesia and sun-

gery. Therefore, in the severely ill patient many factorscan alter DCH independent of nutritional status; correct-ing the underlying medical problem can reverse anergy.

Discriminant Function Analysis

Mathematical equations, developed by use of stepwise

multiple regression analyses of selected “nutritional” pa-

rameters, have been used as an objective measure to iden-tify patients at increased risk for medical complications.28�#{176}However, only the Prognostic Nutritional Index-based

on serum albumin, serum transfernin, triceps skinfoldthickness, and DCH-has been shown to predict clinical

outcome in a prospective evaluation.28

Clinical Assessment

The clinical assessment of nutritional status involves a

focused history and physical examination in conjunction

with selected laboratory tests aimed at detecting specific

nutrient deficiencies and patients who are at high risk for

future nutritional abnormalities. The ability of this ap-

proach to reliably identify patients at increased risk formedical complications has not been evaluated in clinicalstudies.

Subjective Global Assessment

Subjective global assessment (SGA) is a clinical method

for evaluating nutritional status that encompasses histori-

cal, symptomatic, and physical parameters.�#{176}3’ The SGAtechnique determines whether (1) nutrient assimilation hasbeen restricted because of decreased food intake,

maldigestion, or malabsorption, (2) any effects of malnu-trition on organ function and body composition have oc-

curred, and (3) the patient’s disease process influences

nutrient requirements. The findings of the history and

physical examination are subjectively weighted to rank

patients as being well-nourished, moderately malnour-

ished, or severely malnourished and is used to predict their

risk for medical complications. The use of SGA in evaluat-

ing hospitalized patients has been shown to give repro-

ducible results with more than 80% agreement when two

blinded observers assessed the same patient.’#{176}” In pro-spective studies, SGA was a good predictor of complica-

tions in general surgical patients,’#{176} patients undergoingliver transplantation,32 and patients on dialysis.#{176} In onestudy, preoperative SGA was found to be a better predic-tor of postoperative infectious complications than serumalbumin, serum transferrin, DCH, anthropometry, creati-

nine-height index, and the prognostic nutritional index.14

Combining SGA with some of the “traditional” markers of

nutritional status, such as serum albumin, DCH, and crea-

tinine-height index, increased (from 82% to 90%) the abil-ity to identify patients who developed complications but

also increased (from 25% to 30%) the percentage of pa-

tients identified as “malnourished” but who did not de-

velop a postoperative complication. Therefore, combin-

ing nutrition assessment techniques increases sensitivitybut may also increase the number of patients who might

receive unnecessary nutrition support.

Muscle Function

Muscle function tests represent the newest approach

for evaluating nutritional status and include measuring gripstrength, respiratory muscle strength, and the response

ofspecific muscles to electrical stimulation. Starvation andrefeeding causes specific alterations in adductor pollicismuscle response to electrical stimulation. Furthermore,

changes in muscle function induced by nutritional therapy

occur rapidly and before there are any changes in body

nitrogen or protein content.’� In one study, the combina-

tion of an abnormal force-frequency curve and slow re-

laxation rate was more specific and sensitive than other

parameters of nutritional status, such as arm muscle cir-

cumference, serum albumin, and transfernin concentra-tions, as a preoperative predictor of postoperative corn-plications.� Hand grip, respiratory muscle strength, and

relaxation rate of the adductor pollicis have also been

shown to be better than weight loss as a predictor of post-

operative complications.37 It is not known whether restor-

ing muscle function with nutritional therapy improves clini-cal outcome.

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90-100% IBW85-89% IBW80-84% IBW75-79% IBW<75% IBW

Normal range

Underweight

Mild undernutrition

Moderate undernutritionSevere malnutrition


Special Considerations in Pediatric Patients

Nutrition concerns in infants and children differ fromthose in adults primarily because children are growing.

Slowing of normal growth velocity, which equates to slow-ing of normal weight velocity, is an important and early

consequence of undernutrition. However, as in adults,weight loss is a nonspecific marker that may be influenced

by stress and disease. Restoration of normal growth ye-

locity and “catch-up” growth may also reflect improvementin disease status but do not occur in the absence of ad-equate energy and nutrient intake. Day-to-day changes areinterpreted most usefully by comparison of rate of weight

gains with norms for age and sex and in accordance with

goals for catch-up growth. Changes over longer periods,ie, weeks or months, are best evaluated by plotting dataon weight-for-age and weight-for-length (height) percen-

tile charts.”�

Weight should also be assessed as percent of ideal bodyweight. The standards adopted recently by the Cystic Fl-brosis Foundation39 have wider applicability to all infants

and children:

Length (or height) is also evaluated in terms of age-dependent percentiles or Z scores. Low height-for-agepercentiles may be the consequence of factors other thanmalnutrition, such as chronic disease, endocrine disorders,intrauterine growth retardation, or constitutional shortstature.

The importance of chronic malnutrition, as evidencedby low and/or declining length-for-age and/or weight-for-age percentiles, in influencing clinical outcome has beenwell-documented in the developing world. This appliesespecially to recovery from acute diarrhea and to the risk

of persistent diarrhea.4� It may also apply to the risk ofacute respiratory tract infections. There is evidence, al-beit not from PRCTs, that the provision of adequate nutri-tion to improve growth percentiles in children with cysticfibrosis may improve or prevent deterioration in pulmo-

nary function.41”

The younger the infant or child, the more vulnerable heor she may be to adverse effects of malnutrition. Of spe-cial note is the vulnerability of the growing brain. There-

fore, measurement of head circumference should also bea routine component of initial assessment and subsequent

follow-up of the infant and toddler. An initially low or adeclining head circumference percentile together withother indices of malnutrition is an indication to use nutri-tion support.

Monitoring nutrient intake and ability to absorb nutri-ents delivered orally or enterally may be of special impor-tance in the sick child. The younger the infant or child, the

more rapid and severe may be the clinical consequences

of undernutrition and starvation. Therefore, the accept-

able period of complete starvation or of hypocaloric nu-trient intake may be more limited in the child, particularlyinfants.�’

1. Malnutrition is a continuum that starts with mad-equate nutrient intake, followed by a progressive se-

nies ofmetabolic, functional, and body compositional

changes. (B)

2. There is no “gold standard” for determining nutri-

tional status because (a) there is no universally ac-cepted clinical definition of malnutrition, (b) all cur-rent assessment parameters are affected by illnessand injury, (c) it is difficult to isolate the effect of

malnutrition from the influence ofthe disease on clini-

cal outcome, and (d) it is not clear which of the corn-

monly used nutrition assessment techniques is themost reliable because of the paucity of comparative

data. (B)3. Most current nutrition assessment techniques are

based on their ability to predict clinical outcome.

However, the validity of any of these techniques to

truly measure “nutritional risk” has not been provedand the effect of nutritional therapy to influence out-come in patmentsjudged to be “malnourished” has notbeen consistent in PRCTs. (C)

4. Muscle function testing represents a promising newapproach for evaluating the adequacy of nutrient in-take and identifying patients who are at increased riskfor medical complications. However, additional dataand more widespread availability of the technologyare needed before this approach can be incorporatedinto clinical practice. (B)

1. Establish clinical criteria using history and physicalexamination and selected laboratory tests that canidentify patients at risk for malnutrition-induced

medical complications. This requires demonstrating

that a nutrition assessment technique can predict out-come and that nutritional therapy has a beneficialclinical effect in “malnourished” patients. Ethical con-

siderations prevent testing this hypothesis in “se-

verely malnourished” patients.

2. Develop objective technologies for nutrition assess-ment that can identify patients at risk for malnutri-

tion-induced medical complications. This requiresdemonstrating that a nutrition assessment technique

can predict outcome and that nutritional therapy has

a beneficial clinical effect in “malnourished” patients.Two potential areas for future focus are:

a. Muscle function testing

b. Body composition analysis.3. Develop criteria for measuring the nutritional

adequacy of enteral and parenteral nutrition therapy.

GASTROINTESTINAL DISEASES

SHORT BOWEL SYNDROME

Massive resection of the small intestine can cause con-

siderable malabsorption, depending on the amount of

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remaining small intestine, the site of resection, and the

functional status of the remaining gastrointestinal tract.Many patients who have had extensive intestinal resec-tion require total parenteral nutrition (TPN) temporarilyuntil adequate adaptation occurs and allows them to be

transitioned to oral or enteral feedings. The use of TPNpermits these patients to leave the hospital sooner andfacilitates their rehabilitation. A subset of patients withshort bowel syndrome (SBS) cannot survive without long-term TPN because they have such severe impairment innutrient absorption. Patients with ajejunostomy and <100

cm of jejunum and those who have an intact colon but

have <50 cm of jejunum or ileum usually require perma-nent TPN.4546 Providing TPN at home has made a dramaticclinical impact on this patient population. Most patients

with SBS who receive home TPN restore normal bodycomposition, and two-thirds return to school or employ-ment.4748

Aggressive oral or tube feeding can sometimes elimi-

nate the need for TPN. This usually requires ingestion oflarge amounts of fluid, calories, protein, vitamins, andminerals.49 Continuous nighttime tube feedings have beenused successfully to supplement daytime oral intake to

maximize nutrient absorption by the compromised gut.5#{176}

Oral rehydration therapy can be used effectively for pa-tients who cannot maintain fluid and electrolyte homeo-

stasis.5’ These patients often have ajejunostomy and <100

cm of small bowel, a negative sodium balance, and large

gastrointestinal fluid losses.45

1. Enteral and parenteral nutrition support can preventmalnutrition and is essential for survival in selected

patients with SBS. (B)2. Appropriate manipulation of enteral feeding and the

use of oral rehydration therapy can obviate the needfor TPN in selected patients with SBS. (B)

1 . Evaluate importance of growth factors in increasing

residual gut mass and absorptive function in patients

with SBS.

2. Evaluate technologies to improve small-bowel trans-

plantation.3. Evaluate motility patterns and investigate ways to

slow transit and increase intestinal-nutrient contact

time.

INFLAMMATORY BOWEL DISEASE

Protein-calorie malnutrition and specific nutrient defi-

ciencies occur commonly in patients with inflammatorybowel disease (IBD) because ofdecreased nutrient intake,malabsorption, drug-nutrient interactions, and protein-los-

ing enteropathy. Therefore, nutritional therapy is an ac-cepted and important component of the overall manage-ment of patients with IBD by preventing or correctingnutrient deficiencies. Because the usefulness of nutritionsupport as a primary therapy for IBD is more controver-sial, it was the focus of the review by the subcommittee.

Crohn’s Disease-Enteral Nutrition

Many PRCTs have evaluated the clinical efficacy of

defined-formula feeding in patients with Crohn’s disease.Most compare one diet with standard pharmacotherapy,

such as corticosteroids, or one diet with another diet, such

as an elemental (all nitrogen as amino acids) with a

nonelemental formula. Most of these trials suffer from

small sample size, heterogeneous patient populations, a

high percentage of withdrawals in the diet group, and di-ets with variable composition. Three studies,52�’ using

meta-analysis to examine the results of published PRCTs,

concluded that enteral nutrition was not as effective ascorticosteroids (pooled odds ratio, 0.35; 95% confidence

interval, 0.23-0.53 in all studies); overall remission ratesfor nutrition- and steroid-treated patients were approxi-

mately 60% and 80%, respectively. In addition, the pooled

data did not demonstrate an advantage of elemental over

nonelemental formulas (jooled odds ratio, 0.87, 95% con-

fidence interval 0.41-1.83); overall remission rates for pa-tients treated with elemental and nonelemental formulaswere 65% and 61%, respectively. Furthermore, dropout

rates were often high (up to 41%) in patients randomized

to receive elemental formulas.It is not known whether enteral nutrition has a thera-

peutic effect in patients with Crohn’s disease because thereare no PRCTs comparing enteral nutritional therapy witha placebo. However, the overall remission rate of approxi-mately 60% reported after treatment with enteral nutni-tion52� is higher than the 20% to 40% remission rate re-ported in other studies for placebo-treated patients withmild to moderately active disease.5556

Crohn ‘S Disease-Parenteral Nutrition

Several PRCTs have evaluated the importance of bowel

rest and TPN as primary therapy for patients with Crohn’s

disease. These trials demonstrated that bowel rest itself

is not necessary to achieve clinical remission; patients with

Crohn’s disease who were randomized to bowel rest andTPN fared no better than those who received oral or tube

feedings.5759

Colitis (Crohn ‘s and Ulcerative)

Two PRCTs, containing small numbers ofpatients, corn-pared the use of TPN and bowel rest with a regular diet inpatients receiving steroid therapy for acute ulcerative or

Crohn’s colitis.�#{176}6’ There was no difference in frequency

of surgery or duration of required medical treatment be-tween the control and TPN groups. A PRCT comparing

total enteral nutrition with TPN (both used as an adjunctto steroids) was performed in patients with severe acuteulcerative colitis.2 Remission rate and need for colectornywere similar in both groups. However, adverse effects re-lated to nutrition support were significantly less frequentand milder in the enteral nutrition-treated than in TPN-treated patients (9% vs 35%).

Specific Nutrient Therapy

Increasing interest in the role of eicosanoids as modu-lators of inflammation and the immune response has led

to studies of co-3 fatty acids from fish oil in the treatment

of IBD. Conflicting results from various PRCTs have been

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reported showing success and failure� in maintainingclinical remission in patients with Crohn’s disease. Fish

oil supplementation in patients with ulcerative colitis has

resulted in a moderate decrease in disease activityt�and prevention of early but not late relapse.69 There isevidence of a steroid-sparing effect in patients with ul-cerative colitis given fish oil treatment, but it is not ef-fective alone in maintaining remission of disease.

No conclusions can yet be made regarding the use ofglutamine in the treatment of IBD because the experi-

mental evidence is inadequate. Short-chain fatty acid en-ernas have not been effective in the treatment of chronicpouchitis after colonic resection and ileo-anal anastomo-

sis. Recurrence of pouchitis symptoms was prevented in

only 3 of 9 patients with chronic pouchitis who were given

twice-daily butyrate enemas for 2 1 days.7#{176}

Gastrointestinal Fistulas

Although no PRCTs have evaluated the use of nutri-

tion support in patients with gastrointestinal fistulas, it

is likely that the use of TPN in conjunction with bowel

rest has improved clinical outcome. Before the use of

TPN, mortality in patients with gastrointestinal fistulas

was caused by electrolyte and fluid losses, malnutrition,and generalized peritonitis.7’ A retrospective analysis ofpatients with small-bowel fistulas found lower mortalityrates (8% vs 33%), higher spontaneous fistula closures(56% vs 27%), and higher surgical closure rates (92% vs

59%) in patients who received nutrition support than in

those who did not.72Anastomotic fistulas at sites of recent resection in pa-

tients with Crohn’s disease may permanently close with

TPN, bowel rest, and/or octreotide.71 However, fistulas

arising from bowel with active Crohn’s disease are lesslikely to heal. Combining data from many studies sug-

gests that fistula closure following TPN and bowel rest

(35% of patients) is often not maintained after the pa-

tient resumes an oral diet (only 17% of patients main-

tamed fistula closure for more than 3 months).74

Pediatric Patients With IBD and Growth Failure

Growth failure and delayed pubertal maturation arecommon complications in pediatric patients with IBD.Growth faltering is more common in children withCrohn’s disease than in those with ulcerative colitis. TPNor supplementation with liquid formula feeding, givenorally or by intermittent nasogastric tube feedings at

night, can cause marked improvement in both height andweight.7578 In addition, patients treated with elemental

enteral nutrition 1 month out of every 4 months grewbetter and had less-active �

1. Enteral nutrition support is likely to have a therapeu-tic effect in patients with Crohn’s disease, but no

PRCT has compared such nutritional therapy with pla-cebo. (B)

2. Steroid therapy is more effective than enteral nutri-

tional therapy in inducing clinical remission in pa-tients with Crohn’s disease. (A)

3. Noncompliance limits the usefulness of monomeric

and oligomeric diet therapy. (A)

4. Clinical outcome in response to monomeric, oligo-

meric, and polymeric formulas is similar. (A)

5. Bowel rest is not necessary to achieve clinical remis-sion. (A)

6. TPN has not been shown to be an effective primary

therapy for patients with ulcerative or Crohn’s coli-

tis. (A)7. Enteral nutrition or TPN promotes growth in pediat-

nc patients with growth retardation. (B)

1 . Determine the clinical efficacy of nutritional therapyin patients with steroid-resistant or steroid-dependent

Crohn’s disease.

2. Determine the value of perioperative enteral nutri-tion or TPN therapy in decreasing the length of intes-

tinal resection and postoperative complications.

3. Determine the clinical efficacy of specific nutrienttherapy on pouchitis.

4. Evaluate the relationship between dietary factors (eg,potential protein antigens or long-chain triglycerides)and disease activity in patients with Crohn’s disease.

ACUTE PANCREATITIS

Effect ofTPN and Enteral Nutrition on Pancreatic

Secretion

Ingestion of a regular diet during an episode of acute

pancreatitis often causes abdominal pain and increasedlevels of plasma pancreatic enzymes. Therefore, nutrition

support in patients with acute pancreatitis can be givenonly if it does not exacerbate symptoms. This concept has

led to many studies evaluating the effect of various feed-

ing regimens on pancreatic exocrine secretion, with theidea that it is the stimulation of pancreatic secretion that

causes increased pancreatic inflammation and pain.

Most studies suggest that TPN does not stimulate, or

only minimally stimulates, pancreatic secretion.8’�T Intra-

venous lipids are usually well-tolerated.�89 However, sev-

eral cases have been reported in which lipid infusionscaused pancreatitis, presumably because of hyper-

triglyceridema.�#{176}�

The effect ofenteral feeding on pancreatic secretion is notclear because data are conflicting. hi some studies, jejunalfeeding ofalow-fat elemental formula did not stimulate pan-

creatic secretion,1�5 while others have found increased pan-creatic enzyme secretion duringjejunal feedingY�98

Mild or Moderate Pancreatitis

Approximately 80% to 90% of patients with acute pan-

creatitis have mild or moderate disease, as judged by

Ranson criteria’� or computed tomographic scanning. ‘#{176}#{176}

These patients can be managed with standard supportivemeasures and do not need special treatment. There is noevidence that aggressive enteral nutrition or TPN therapychanges the natural course of the illness in patients withmild or moderate disease. A PRCT evaluating the use ofTPN in patients with mild to moderate disease found no

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beneficial effects on morbidity or ty’#{176}’In fact, pa-

tients given TPN had greater insulin requirements and ahigher incidence of catheter-related infections than the

control group. Recently, McClave et al’#{176}2demonstrated that

jejunal tube feeding of a hydrolyzed oligomeric formulawas well-tolerated and was less expensive than TPN. How-ever, only 82% of patients who received enteral nutrition

reached their caloric goal, compared with 96% of patientsgiven TPN. Clinical outcome was the same in both groups.

Severe Pancreatitis

Approximately 10% to 20% of patients with pancreatitis

have severe disease and are at high risk for medical corn-plications. These patients may have increased nutrient

requirements because of increased rates of energy expen-

diture and protein �03, 104 Negative nitrogen bal-

ance has been associated with adverse clinical outcome.In one study, patients with pancreatitis who were in nega-tive nitrogen balance had a 10-fold increased mortality rate

than those in positive balance.’#{176}5 However, the relation-ship between nitrogen balance and outcome may simply

reflect the relationship between nitrogen balance and se-verity of disease.

No PRCTs have evaluated the clinical efficacy of nutri-tion support in patients with severe pancreatitis. The useof TPN has been reported in studies that used historicalcontrols,�3”#{176}�’#{176}7had no controls,’#{176}8 or contained only a sub-

set of patients with severe disease.’#{176}5”#{176}#{176}”#{176}Furthermore,

severe pancreatitis was usually defined by Ranson crite-

ria rather than more recently used radiologic approaches,which may be more sensitive in identifying patients with a

poor prognosis.” The safety and clinical efficacy of tubefeedings in patients with severe pancreatitis is not known.Jejunal feedings of an elemental formula were toleratedwithout an exacerbation of pancreatitis in patients whowere fed soon after surgery for complicated pancreatitis. �12

However, two patients died from complications related tothe placement of the needle jejunostorny.

Complicated Acute Pancreatitis

The most common serious complications of acute pan-creatitis are pancreatic fistulas and ascites. Data on the useof enteral nutrition or TPN in these situations are hi the formof case reports or uncontrolled retrospective series.81”4Nutrition support was given after the initial bout of acute

pancreatitis subsided and complications developed. Nearlyall patients with fistulas were treated with TPN, and over

90% ofthe fistulas closed. Pancreatic ascites resolved in 4 of5 patients, and enteral nutrition was used in two patients.”5

Pediatric Patients

The incidence of pancreatitis in children is low corn-pared the incidence in adults, and no PRCTs have evalu-ated the potential benefits of nutritional therapy for acutepancreatitis.

1. Neither enteral nutrition nor TPN has a beneficialeffect on clinical outcome in patients with mild ormoderate pancreatitis. (A)

2. Patients who have a protracted clinical course, such

as those with severe disease or complications, oftenrequire nutrition support to prevent the adverse ef-fects of nutrient deprivation. The timing, route, andnutrient formulation for optimal nutritional therapy

are not clear because of the paucity of clinical trials.(C)

3. Enteral feeding can be safely administered to patients

with pancreatitis. Jejunal tube feeding is often toler-

ated without an exacerbation ofsyrnptoms in patients

with mild or moderate disease and in patients who

have had surgery for complications of pancreatitis.

(A) However, the site of feeding (gastric vs duodenalvsjejunal) and the nutrient formulation (elemental vspolymeric; low fat vs normal fat) that cause the leastrisk for exacerbating disease symptoms are not

known.

4. The use of intravenous lipid emulsions is safe in pa-

tients with acute pancreatitis, provided hyper-triglyceridernia (>400 rng/dL) is avoided. (A)

1. Controlled studies are needed to evaluate the clini-

cal efficacy and cost-effectiveness of enteral nutri-tion and TPN in patients with severe pancreatitis, as

defined by both clinical evaluation and modern im-aging techniques.

2. The importance of feeding site (oral, gastric, duode-

nal, andjejunal) and formulation (elemental and low

fat) in determining tolerance to enteral feeding shouldbe evaluated in patients with protracted severe orcomplicated pancreatitis.

LIVER DISEASE

Protein-energy malnutrition is common in patients with

advanced chronic liver disease. However, assessment ofnutritional status in this patient population can be difficultbecause of the confounding influence of liver disease onthe traditional markers of nutritional status. In a retrospec-

tive study, the severity of “protein-energy malnutrition” cor-

related with the severity of liver disease and clinical out-

1 16 Furthermore, improvement in nutritional status

after 30 days ofhospitalization was associated with reduced

mortality, although it is not clear whether improved nutri-

tional status affected survival or whether clinical improve-ment affected the markers of nutritional status.

Alcoholic Hepatitis

The clinical efficacy of peripheral parenteral amino ac-

ids in alcoholic hepatitis has been evaluated by several

groups (cf, McCullough et al”7). Most studies found im-proved histology or liver biochemistries but no consistent

decrease in morbidity or mortality in patients who receivedparenteral amino acids. Some studies evaluated the useof nutritional therapy in conjunction with steroids in pa-tients with alcoholic hepatitis. One PRCT compared pa-tients randomized to peripheral parenteral nutrition (PPN)(50 g of glucose and 35 g of amino acids daily),oxandrolone, the combination, or no treatment for 2 1 days.Child’s Pugh score improved significantly in those who

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received PPN plus oxandrolone, but mortality rates weresimilar in all groups.”8”9 Mendenhall et al’2#{176}studied theeffect of a combination of oxandrolone with a branched-chain amino acid (BCAA)-enriched enteral supplement inpatients with moderate or severe alcoholic hepatitis. Onan intention-to-treat basis, mortality rates were similar inboth treated and control groups of patients with severealcoholic hepatitis. In apost hoc subgroup analysis, involv-

ing only those with markers suggesting either advancedliver disease or moderate malnutrition, liver function im-

proved and 1- and 6-month mortality rates in patientstreated with nutritional therapy.

Alcoholic Cirrhosis

Several PRCTs have found that enteral nutrition sup-

port in patients hospitalized for complications of cirrho-sis was well-tolerated, and improved liver function, hepaticencephalopathy, and Child’s score.’21’24 In addition, onestudy found a trend toward decreased in-hospital mortal-

ity in patients with cirrhosis and protein-calorie malnutri-

tion who were given enteral tube feeding with a formulaenriched with BCAAS (mean intake = 2115 kcal/day; mor-

tality 12%) compared with an ad lib hospital diet (meanintake = 1320 kcal; mortality 47%).124 However, the differ-ence between groups may have been exaggerated by theunusually high mortality rate observed in the control group.

Acute Hepatic Encephalopathy

The clinical efficacy of BCAA-enriched TPN solutions inpatients with acute hepatic encephalopathy has been evalu-ated in 9 PRCTs. These trials were reviewed by using meta-analysis to pool data across studies. ‘� Patients who received

BCAA-enriched solutions demonstrated a statistically sig-nificant improvement in recovery from encephalopathyduring short-term (7- to 14-day) nutritional therapy. Con-

siderable heterogeneity in mortality rates between studiesprecluded meaningful aggregation of mortality data. In ad-dition, the design of most ofthe studies may have inadvert-ently favored the treatment group. The control groups usu-ally received suboptimal, and possibly harmful, nutritionsupport consisting ofhigh-dextrose solutions without amino

acids. Only one study compared BCAA-enriched TPN witha standard amino acid TPN solution, and this study did notdemonstrate a beneficial effect ofBCAA-enriched solutions.None of the studies reported on complications associated

with nutritional therapy and none evaluated whether short-term benefits of nutritional therapy led to a long-term re-duction in complications.

Chronic Hepatic Encephalopathy

Studies of the efficacy of enteral BCAA formulas vs con-ventional protein sources for treatment of chronic hepaticencephalopathy have produced conflicting results. How-ever, the studies with the largest number of patients and

least chance for a type II statistical error tend to demon-strate a beneficial effect of BCAAS on protein toleranceand symptoms of encephalopathy, particularly in protein-intolerant �7,126

Pediatric Patients With Liver Disease

Pediatric patients with liver disease differ from adultsin several ways: (1) fewer pediatric patients have liver dis-

ease; (2) the causes of acute and chronic liver diseases

are more varied in children; (3) a larger proportion of pe-diatric patients have inborn errors of metabolism, biliary

tract disease, primary infections, and autoimmune disor-ders’27’28; and (4) the higher anabolic needs for growthcoupled with the catabolic effects of liver disease mayresult in more nutritional deficiencies. No PRCTs evaluat-ing the clinical efficacy of nutritional therapy in childrenhave been performed.

1. Providing adequate enteral nutrition or TPN therapy

improves some parameters of liver function in pa-tients with chronic alcoholic liver diseases. (A)

2. The aggregate of data are inconclusive to determinewhether enteral nutrition or TPN decreases morbid-ity and mortality in patients with alcoholic liver dis-

eases. (A)

3. BCAA-enriched TPN increases recovery from acute

hepatic encephalopathy compared with high-dextrose

solutions that do not contain amino acids; BCAA-en-riched solutions have not been shown to be superior

to standard amino acid formulas. (A)4. In patients who are protein-intolerant because of

chronic or latent hepatic encephalopathy, BCAA-en-riched formulas permit greater protein intake with-

out inducing encephalopathy than do standard pro-

tein formulas. (A)

1. Determine if enteral nutrition support alters health

care costs and long-term clinical outcome in patients

with (a) alcoholic hepatitis and (b) cirrhosis.

WASTING DISORDERS: CANCER AND AIDS

Wasting disorders are characterized by involuntary loss

of body weight and lean tissue in the setting of a chronicillness. Although wasting can occur in any ill patient, the

subcommittee focused its report on patients with cancer

and AIDS because of the prevalence and clinical impor-tance of cachexia in these disorders.

Many studies have demonstrated a direct relationshipbetween mortality and loss of either body weight or lean

body mass (LBM). 129-132 Furthermore, starvation-inducedmalnutrition can affect strength, ambulation, exerciseperformance, and cognitive function,’33 which can im-pair daily activities and quality of life. The associationbetween wasting and death has led to the assumptionthat prevention or reversal of wasting will delay or pre-vent death from AIDS or cancer; however, there are nopublished observations providing direct evidence that

wasting is a cause of death or that reversal of wastingimproves outcome. Therefore, the association betweenwasting and adverse outcome may reflect an associa-tion between wasting and severity of illness, rather thana cause-and-effect relationship. In nonmedical settings,such as prison hunger-strikers and victims of famine,

there is a causal relationship between weight loss and

mortality.

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The ability to replenish LBM with nutritional therapymay depend on the etiology of wasting. Two factors cancause wasting in patients with cancer or AIDS: (1) inabil-ity to assimilate nutrients, caused by gastrointestinal ob-

struction, rnalabsorption, and anorexia; and (2) abnormali-ties in rnacronutrient metabolism, caused by alterations

in regulatory hormones and cytokines. Patients with can-cer or AIDS may have metabolic derangements that in-crease LBM loss or inhibit its repletion. Loss of LBM as apercentage oftotal weight loss is often disproportionatelyhigh compared with a pure semi-starvation model.’2t’ Fur-thermore, when nutrition support results in weight gain,it is often the net result of increased fat deposition andincreased body water, not an increase in LBM. ‘�‘ Body cellmass is more likely to be restored by nutritional therapyin patients with simple macronutrient deficiency than inthose who have primary alterations in metabolism.

CANCER

At least 40 PRCTs have been reported evaluating theclinical efficacy of nutritional therapy in patients with can-cer receiving chemotherapy or radiation therapy (cf, Kleinand Koretz’35). Two meta-analyses, which pooled the re-

sults from many of these trials, concluded that the use of

adjunctive nutrition support did not demonstrate benefi-

cial effects.’36’37 Moreover, the pooled data suggested, onthe basis of higher infection rates, that TPN was harmfulin patients receiving chemotherapy. However, seriousshortcomings in the design of the published PRCTs maylimit the applicability of these conclusions to current pa-tient care. The most important criticisms of the PRCTsinclude the following: (1) patient populations were het-erogeneous and included patients with different tumortypes and stages of disease, which may have masked ben-eficial effects of therapy in certain subgroups; (2) manystudies excluded patients with severe malnutrition, thusexcluding those who might have shown the greatest ben-efit from nutrition support; patients with normal pretreat-ment nutritional status-who may have been unlikely toshow a beneficial effect of nutritional therapy-were in-cluded; (3) the specific type of cancer therapy varied be-tween studies and often was not consistent within a study;

(4) the composition, timing, and duration of nutrition sup-port may not have been optimal (for example, excess glu-cose or lipid in many studies may have affected immunefunction and increased infection risk); (5) the use of corn-plication and mortality rates alone as outcome measuresis inadequate because these are less likely to be affected

by nutritional therapy than are other important clinicalendpoints, such as LBM accrual, growth in children, func-

tional status, and quality of life, which were rarely evalu-ated; (6) most studies involved the use of TPN, which ismore likely to have infectious complications than otherroutes ofnutrition support; and (7) the sample size of eventhe pooled analyses may have been inadequate to detectsmall, but clinically important, benefits of nutrition sup-port.

Cancer Chemotherapy

Eighteen PRCTs evaluated the use of TPN in patientsreceiving chemotherapy (cf, Klein and Koretz’�). TPN wasusually given for a short period (3 to 6 weeks) before or

during the course of chemotherapy. The use of TPN usu-ally caused an increase in body weight, but the bodycompartment(s) responsible for the increase in weight was

not determined. Overall, the use ofTPN did not affect sur-vival and did not decrease hematologic or gastrointesti-nal toxicity from chemotherapy. Half of the studies re-ported infectious complications; infection rates werehigher in patients who received TPN, with a pooled oddsratio four times that of the control group.”6”7 No study

included a sophisticated measure of the effect of nutri-tion support on function, performance, or quality-of-life.

Seven PRCTs examined the use of enteral nutrition

therapy given either as oral supplements or as tubefeedings (cf, Klein and Koretz’35). These studies varied inthe composition, timing, and duration of enteral nutrition.No obvious therapeutic benefits in survival, tumor re-

sponse, or chemotherapy toxicity were observed in thesestudies. No PRCTs comparing TPN to enteral nutritionwere found. The use of home TPN or enteral therapy hasalso not been evaluated by PRCTs.

One PRCT evaluated the effectiveness oforal glutanunesupplementation in managing oral mucositis in patientsreceiving chemotherapy for metastatic gastrointestinalcancer.’38 ��though the supplement was well-tolerated, itdid not increase plasma glutarnine concentrations andfailed to affect mucositis.

Radiation Therapy

Data were inconsistent as to the overall merits of TPNor enteral nutrition support in patients receiving radiationtherapy. Most studies contained a small sample size andfailed to stratify by disease, pretreatment group differ-ences, nutritional status, or concomitant therapies. Four

PRCTs studied the clinical efficacy of TPN in patients re-ceiving radiation therapy for treatment of abdominal orpelvic cancers (cf, Klein and Koretz”�). Overall, there wereno definitive differences in survival or radiation therapy-induced side effects between patients receiving nutritionsupport and the control group.

Seven PRCTs evaluated the use of enteral nutritional

therapy (cf, Klein and Koretz”�). Oral or enteral nutritionaltherapy decreased the amount ofweight lost during radia-tion treatment. There were fewer hernatologic or gas-trointestinal side effects of radiation therapy in nutrition-ally treated patients who received radiation for abdominaland pelvic cancer, but there were more in one study ofpatients receiving radiation therapy for head and neckcancer. Nutritional therapy did not affect survival, whichwas reported in only two studies, and the effect of nutri-tional therapy on functional ability was not evaluated.Some studies reported greater weight gain or less weightloss in patients who received nutrition support, but reli-

able analysis of body composition was not performed.

Bone Marrow Transplantation

Bone marrow transplantation results in very negativenitrogen balances and a disproportionately greater loss oflean body mass than body weight or fat losses. A subset ofpatients who have had bone marrow transplantation de-velop considerable gastrointestinal dysfunction and re-quire TPN for survival. Two PRCTs studied the use of stan-

dard nutrition support in patients treated with bone

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marrow transplantation, which included patients with bothallogenic and autologous transplants (cf, Klein andKoretz’35). There was no stratification by presence or ab-sence of malnutrition. Myelosuppression, incidence ofgraft-vs-host disease, length of hospital stay, and bacter-ernia were not decreased by providing TPN. Patients givenTPN maintained or increased body weight compared withcontrol patients, but reliable measures of body composi-tion were not performed and nitrogen balance remainednegative. In one study”9 an impressive improvement inmean survival (21-month survival) was reported in patientswho received TPN compared with control patients (7-month survival). However, the survival advantage was notevident until 6 months after transplantation. In the sec-ond ri’40 patients were randomized to receive either TPNor enteral nutrition. More than two-thirds of the patientsrandomized to enteral nutrition were given additionalparenteral intravenous amino acids to meet their estimated

requirements. Survival was not different between the twogroups.

Two PRCTs evaluated the potential benefit of glutamine-

enriched TPN compared with standard TPN. In one study’4’100-day survival rates were the same in both groups, butthe patients who received glutamine had a lower rate ofinfection, shorter duration ofhospitalization, and improved

nitrogen balance. In contrast, in the second trial’42 the rateof survival, rate of infections, and duration of hospitaliza-tion was not significantly different between groups whenall randomized patients were included in the analysis.However, when outliers were excluded, the length of hos-pital stay was significantly shorter for patients receiving

the glutamine-enriched formulation.

AIDSA reliable assessment of the clinical efficacy of TPN or

enteral nutrition support in patients with AIDS is difficultbecause so few studies have evaluated this issue. Further-more, most of the reported studies contained small num-bers of subjects and few were designed as a PRCT.

Retrospective and prospective uncontrolled experiences

have reported conflicting results regarding the effect ofTPN or oral/enteral feeding on body weight and body corn-

position in patients with HIV infection.’4’’5#{176} The differ-ences observed between studies may be related to the pres-ence of underlying illness. Home TPN did not cause anincrease in LBM, despite increases in weight and fat in 12AIDS patients; post hoc analyses suggested that LBM in-creased in five patients who had anorexia-induced weightloss but not in seven patients who had systemic infec-

�48 Percutaneous gastrostomy tube feeding in eightmalnourished patients with anorexia increased LBM,’49whereas enteral feeding did not prevent weight loss in pa-tients who had concomitant secondary infections. ‘�#{176}

Several studies have evaluated the use of oral formulasfortified with nutrient(s) designed to modify the physi-ologic response to the disease. A 6-month PRCT compareda peptide-based oral supplement containing additionalmedium-chain triglycerides, (�3-carotene, and soluble fi-ber with a standard supplement and found better weightmaintenance and fewer hospital admissions (betweenmonths 3 and 6 only) in those who received the specialtyformula.’5’ An 8-month controlled, double-blinded, ran-domized, crossover design was used to evaluate an oral

formula supplemented with a-linolenic acid, arginine, and

RNA compared with a control supplement in 10 patients

with symptomatic HIV infection.’52 Modest weight gainoccurred when patients were given the specialty formula,but more important clinical parameters, such as morbid-

ity, mortality, and quality-of-life, were not evaluated. Twostudies that evaluated w-3 fatty acid (“fish oil”) supple-mentation did not demonstrate clinical benefits, althoughthe studies were not designed to measure clinical out-

‘�3,’#{176}’

Pediatric Patients

Children with cancer have marked weight loss duringinduction therapies.’55 Although both survival and qualityof life are associated with measures of nutritional sta-tus,’�”57 few PRCTs have evaluated the efficacy of nutri-

tional therapy in children with cancer. In one PRCT, no

improvement in clinical outcome was observed when TPNwas given as routine adjuvant therapy, in the absence ofpretreatment malnutrition; weight gained was fat, not leantissue, and crude performance measures did not im-

�58 In a small subset of severely malnourished chil-dren (n=4), however, improvement in performance statuswas observed in patients who received TPN. In uncon-trolled studies, children who are malnourished prior totherapy showed weight gain and increased muscle mass

when given TPN,’59 but clinical or functional outcomemeasures were not reported. In well-nourished children,weight gained during TPN is predominantly fat.’�”�#{176}

Children with AIDS frequently exhibit stunting and de-creased weight for height. No PRCTs evaluating the use ofnutrition support in children with AIDS have been re-ported. Uncontrolled trials of enteral nutrition supportsuggest that nutritional therapy increases body weight;however, the increase in weight is mostly due to an in-crease in body fat without a change in LBM or 16�,�62

No PRCTs have evaluated clinical or functional outcomes,

home TPN, or long-term oral/enteral nutrition support.

Long-Term Management ofChronic Wasting

The important issue of long-term management of wast-ing patients who are unable to eat because of their under-lying disease or therapy has not been carefully addressedin clinical studies. It is possible that home nonvolitionalfeeding can improve quality of life and survival in appro-

priately selected patients. However, there is a paucity ofobjective data that address this hypothesis or that helpdetermine which patients with cancer or AIDS should beconsidered for long-term nutritional therapy.

The use of home TPN in the United States more thandoubled between 1989 and 1992, in large part because ofthe increased use in patients with cancer, who accounted

for 46% of new home TPN patients in 1989.’� In contrastto patients with benign diseases, less than half of the pa-tients receiving home TPN who had cancer or AIDS werealive at 6 months, and only 20% and 10%, respectively, werealive at 1 year. A recent PRCT provided 2 months of home

TPN to patients with AIDS who had lost > 10% oftheir body

weight had diarrhea but did not have a secondary infec-tion; the results showed that this treatment caused an in-crease in body weight, body cell mass, Karnofsky index,and subjective feeling of health compared with a decline

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in these parameters in patients randomized to receive di-etary counselling only. ‘� However, the rate of rehospital-

ization and survival was the same in both groups.Gastrostorny or jejunostomy tube feedings are associ-

ated with fewer complications and are less expensive thanfeeding with home TPN. Prospective uncontrolled stud-ies and retrospective data suggest that long-term gastros-

tomy tube feedings are well-tolerated, are associated withfew complications, and may prolong survival in patientswith cancer or MDS’6��”�’ However, no PRCTs have stud-ied this issue.

1. The routine use of adjunctive short-term enteral nu-trition or TPN does not decrease complications ormortality in patients who are receiving chemotherapy

or radiation therapy for cancer. (A) However, manyof the reported PRCTs have serious limitations instudy design that may limit their applicability to cur-rent medical practice. (C)

2. Long-term enteral nutrition or TPN may be benefi-

cial by maintaining hydration, providing nutrients,increasing comfort, and improving survival in patientsunable to eat or absorb adequate nutrients for a pro-longed period. (B) However, no PRCTs have evalu-ated this issue.

3. Use of TPN is associated with an increased rate ofinfection (including non-catheter-related infections)in patients treated with chemotherapy. (A) It is pos-sible that technical advances in line insertion, im-

proved methods of catheter care, and the trend to-ward lower calorie and/or fat administration maydecrease the incidence ofTPN-induced infections butthis has not been proven in PRCTs. (C)

4. Standard TPN given after bone marrow transplanta-

tion does not decrease treatment toxicity, graft-vs-host disease, or bacteremia; does not increase leantissue accrual; and does not affect short-term (<6-month) survival. However, one PRCT found short-term TPN may increase long-term survival (>6-month)and decrease the rate of tumor relapse. (A)

5. The impressive loss of tissue mass and function that

occurs in patients with wasting disorders makes res-toration of disordered body composition a reason-able clinical goal, until definitive studies are per-formed to evaluate this hypothesis. (C)

6. TPN, enteral, and oral nutrition support may prevent

or reverse weight loss and replenish body cell massin patients with AIDS who have poor food intake orrnalabsorption and do not have an active opportunis-

tic infection. Nutritional therapy does not have ben-eficial effects on body composition in patients withAIDS who have systemic infection. (B)

7. Despite the striking weight loss or stunting that of-

ten occurs in children with cancer or AIDS, routineuse of TPN in these children does not improve qual-ity of life, growth, or survival. (B) Nutrition supportmay increase muscle mass in children who are mal-nourished prior to therapy. (B)

8. Many decisions relevant to nutrition practice for pa-

tients with wasting disorders cannot be based solely

on definitive, research-based evidence because of theabsence of clinically relevant PRCTs. (C)

1 . Perform PRCTS to determine the effect of enteral andparenteral nutritional therapy on body composition,functional status, quality oflife, and clinical outcomein defined populations of malnourished patients withcancer or AIDS.

2. Determine objective criteria that can identify wast-

ing patients who are likely to achieve long-term ben-efits from adjunctive nutritional therapy.

3. Evaluate the potential benefits of specialized nutri-

tional formulas supplemented with glutamine, argin-me, ribonucleic acids, w-3 fatty acids, or other nutri-ents.

4. Determine (1) the optimal means for measuring body

composition in patients with wasting diseases and (2)the relationship between lean body mass and clinicaloutcome (including muscle function, psychosocialfunction, quality of life, performance status, morbid-ity, and mortality) in patients with cancer or AIDS.

CRITICAL ILLNESS

Evaluating the clinical efficacy of nutrition support isparticularly difficult in patients requiring intensive care.This is partly due to the difficulty ofassembling large nurn-bers of patients with the same diagnosis and severity ofillness and comparable nutritional status, as well as con-

ducting a clinical trial in the face of multiple therapies thatare altered according to a changing clinical condition. Thetheoretical value of nutrition support in patients with criti-cal illnesses is to provide exogenous substrates to meetprotein and energy requirements, thereby protecting vitalvisceral organs and attenuating breakdown of skeletalmuscle. The potential benefits of nutrition support wereexamined in adult patients who had the following illnesses:trauma, sepsis/systemic inflammatory response syndrome(SIRS), multiple organ dysfunction syndrome (MODS),thermal injury, acute lung injury (ALl), or acute renal fail-ure. The effect of nutrition support in critically ill childrenwas not reviewed because there are no PRCTs evaluatingthis issue. Given the differences between adults and chil-dren in their tolerance to the adverse effects of malnutri-tion and the need for growth, results from studies in adultsshould not be extrapolated to pediatric patients.

TRAUMA (BLUNT TRAUMA/HEAD TRAUMA)

No studies have compared giving nutrition support with

not giving nutrition support to traumatized patients. Twostudies assessed whether early enteral nutrition wouldbenefit patients with trauma.’6”7#{176} In one study’#{176}the pa-tients in the control group who were not eating within 5days ofthe start ofthe trial were begun on TPN. The otherstudy’7#{176}examined the use of a commercial enteral diet,which was provided after 72 hours; the early-fed grouphad a greater number of infections, without differences inother clinical outcomes (eg, days on mechanical ventila-tion, length ofstay, etc). Four studies compared TPN with

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enteral nutrition support in patients with non-headtrauma.’71’74 Three ofthese studies’72’74 demonstrated thatpatients given enteral nutrition had fewer infections thanthose given TPN. It is not clear from these studies whetherenteral nutrition provides a specific benefit, or whether

TPN is associated with increased infections, which hasbeen noted in other conditions.’�’37’7�’77 Patients who re-ceived TPN were fed more calories then those random-ized to receive enteral nutrition, which may have contrib-uted to the increased infection rate. There is no goodevidence that solutions enriched with BCAAS decreasemorbidity or mortality’713”#{176} or that the administration ofalbumin has clinical benefits in patients receiving TPN.’�’�

Several studies have compared TPN with enteral nutri-tion in patients with head trauma.’87’9’ In one, all 20 pa-tients who received TPN lived, whereas 8 of 18 patients who

received nasogastnc feeding di’87 However, the increasedmortality may have been secondary to pulmonary aspira-tion of gastric contents related to gastroparesis associatedwith head injury. When the same investigators repeated thestudy, this time using postpyloric feeding, no differenceswere observed between enterally and parenterally fedgroups.” An alternative explanation is that the originalstudy actually assessed the effect of adequate (TPN) vs in-adequate (enteral nutrition) feeding, because of the time itnormally takes a critically ill patient to meet caloric needswith enteral gs’87 The failure to see a difference inthe second study could be because the investigators werenow able to successfully meet caloric needs earlier withenteral feeding and thus both groups received adequate nu-trition support. Other studies have failed to demonstratedifferences in morbidity or mortality in comparisons of TPNwith postpyloric enteral nuthtion’� or even with nasogasthc

dings89#{176}” Grahm et al’11� in a quasi-randomized prospec-tive trial, observed fewer infections in 16 patients who re-ceivedjejunal tube feedings within 72 hours oftheir admis-sion compared with another 16 who received gastric tubefeedings after 72 hours.

Immunonutrition

Several PRCTs have evaluated the effects of variousenteral formulas supplemented with selected nutrients(co-3 fatty acids, arginine, nucleic acids, glutamine) on clini-cal outcome.”#{176}’98 Two studies’�’3’94 compared an enteraldiet containing increased amounts ofw-3 fatty acids, argi-nine, and ribonucleic acids to a standard enteral formuladiet. The authors from both studies concluded that infec-tious complications and hospital lengths-of-stay were de-creased in patients who received the modified formula,but these claims were based on post hoc subgroup dataanalyses. In one study’94 the recipients of the modified for-mula showed a trend toward a higher mortality rate. Arecent abstract compared the use of diet with a different“control” diet; the data suggested that the recipients ofthe experimental diet had fewer complications and whencomplications occurred, they were less expensive to man-

198 Another PRCT found that patients given a modified

formula diet containing additional glutamine, arginine,nucleic acids, and w-3 fatty acids had less multiorgan fail-ure than those given a standard amino acid (SAA)-basedelemental diet.’95 A recent trial comparing this prepara-tion with a protein-supplemented standard enteral formulafound that patients who received it had fewer major infec-

tious complications.’� One other trial, assessing anotherformulation containing a-linoleic acid, �3-carotene, andarginine, is difficult to interpret because of a serious break-down in the randomization procedure.’97

SEPsIs/SIRS/MODS

One study compared enteral nutrition support consist-ing of a BCAA-based solution with a formulation contain-ing SAAs; no difference in mortality was seen betweengroups.’99 Four trials compared BCAA- with SAA-basedTPN2#{176}#{176}2#{176}3;only one demonstrated any difference in clini-

cal outcome, a decrease in mortality in the group receiv-ing the BCAA-enriched formula.2#{176}#{176}However, the data fromthis trial are only available as an abstract. Finally, one trialfound no differences between groups given equivalentnutrients by parenteral or enteral routes.2#{176}�

THERMAL INJURY

Many PRCTs have examined nutrition support in patientswith thermal �j�2a5�2I2 One study, containing a total of only16 patients, found no statistically significant differences in

survival between patients given parenteral fat and glucose

with amino acids compared with those given fat and glucosewithout amino acids.207 One study examined TPN with solu-

tions containing either 45% or 19% of amino acids as BCAAS

and failed to demonstrate any differences in survival betweenthe two study groups.2#{176}” Chiarelli et al2#{176}�’found no significant

differences in infections or mortality in patients fed bynasogastric tube immediately after admission compared withthose fed at least 48 hours later. A study examining standardenteral nutrition support with and without additional whey

protein demonstrated that patients who received the higherproteinlevels had less morbidity and greatersurvival.21#{176} How-ever, the interpretation of these results is complicated be-

cause more patients in the low-protein group than in the high-protein group received supplemental parenteral nutrition.

Jenkins et al21’ demonstrated that patients who received en-tera.l nutrition throughout an operative procedure toleratedthe feedings and had fewer postoperative wound infections.Herndon et al205’2#{176}t’have reported two trials in patients with50% surface area bums who were randomized to receive en-teral nutrition as tolerated with or without additionalparenteral nutrition. The mortality rates in patients who re-ceived additional parenteral nutrition were numericallyhigher than in those fed only enterally, and in one study2#{176}�thedifferences achieved statistical significance. However, thepatients who received parenteral nutrition in addition to en-teral feedings may have received excessive amounts of en-ergy. Garrell et al212 compared three enteral nutrition feedings

containing 15% (with or without w-3 fatty acids) or 35% fat;

the patients who received the lower fat formulations had alower frequency ofpneurnonia. Finally, one trial compared aspecially prepared enteral formulation containing whey,glutamine, arginine, and w-3 fatty acids with two differentstamiard enteral diets.213 Patients who received the speciallyprepared formula had a shorter duration of hospitalizationand fewer infections.

ACUTE LUNG INJURY

High-fat, low-carbohydrate intake has been recom-mended for patients with pulmonary diseases to decreasecarbon dioxide production. Only one PRCT has shown a

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beneficial effect of a diet high in fat and low in carbohy-drate; Al-Saady et al214 found that patients given a high-fat,low-carbohydrate diet had a 16% decrease in PaCO9 andspent 62 hours less time on mechanical ventilation thanpatients who received standard feeding. Van den Berg etal215 were not able to find a decrease in ventilator time inpatients receiving a high-fat, low-carbohydrate diet, even

though their patients did exhibit a significant reduction inCO2 production. In fact, Battistella et a1216 found thattrauma patients randomized to receive a lipid-free formulafor the first 10 days of their hospitalization spent less time

on the respirator, in the ICU, and in the hospital than pa-tients randomized to receive TPN containing lipids. How-ever, the patients given lipids received more total cab-

ries. In 40 neonates with respiratory distress syndrome,Gunn et al2’7 were not able to demonstrate a statisticallysignificant clinical benefit of TPN; however, the mortalityrate in the group receiving TPN (15%) was half that of thecontrol group (30%), raising the possibility of a type II sta-tistical error.

ACUTE RENAL FAILURE

No PRCTs have assessed the clinical efficacy of enteral

nutrition support, but several have evaluated the use ofTPN in patients with acute renal failure.21�222 All studiescontained limitations in design that make it difficult toassess the effect of nutritional therapy on morbidity and

mortality. The numbers of patients studied in these trialswere small, and most studies were primarily designed toevaluate the metabolic effects of feeding rather than mor-bidity and mortality. Moreover, some ofthe control groupswere not “true” controls (ie, a group not receiving any formof TPN) and received isocaloric quantities of TPN with-out amino acids.21�22#{176}Only one study218 showed a statisti-cally significant difference in a clinical outcome betweengroups-a greater recovery rate from acute renal failurein patients given TPN containing nitrogen in the form of

essential amino acids only compared with a control groupwho received TPN without any amino acids. In addition,two studies2’8’22#{176}showed arithmetically, but not statisticallysignificant, increased survival rates in patients who re-ceived TPN containing nitrogen in the form of essentialamino acids only compared with a control group givenequicaloric amounts of dextrose. Three trials22#{176}222corn-pared TPN containing nitrogen as essential amino acidsalone with TPN containing both essential and nonessen-tial amino acids. Although the numbers of patients stud-ied were small, the recovery and survival rates were allarithmetically greater (but not statistically significant) inthe group who received only essential amino acids.

The use of continuous filtration techniques (eg, continu-ous venovenous hemofiltration or continuous arterio-venous hemofiltration with or without hemodialysis orhemodiafiltration) usually leads to increased tolerance ofamino acid and protein intake.2� Moreover, the catabolicstate engendered by the severe comorbid conditions ofmany of these patients, the losses of nutrients throughdialysis or ultrafiltration,224225 and the possible catabolicstress of the hernodialysis or continuous filtration proce-dure itself may increase the nutritional demands of thesepatients. Thus it is anticipated that patients with acute

renal failure who are undergoing dialysis or ultrafiltrationtherapy may need increased quantities of nutrients, includ-

ing essential and nonessential amino acids. However, theclinical benefits of providing such nutrients have not yetbeen demonstrated in PRCTs.

1. Critically ill patients are hypermetabolic and have in-creased nutrient requirements. Although it has beenassumed that nutrition support is clinically beneficialin this patient population, this hypothesis has not been

tested by well-designed clinical trials. (C)

2. In the absence of carefully designed clinical trials, therationale for nutrition support is based mostly on clini-cal judgment, and nutrition support is considered inpatients who are unlikely to consume adequate nutri-ent intake for a “prolonged” period. Although it is notknown howlong a critically ill patient can tolerate lackof nutrient intake without adverse consequences, the

loss of lean tissue that occurs in severely catabolic

patients (20 to 40 g ofnitrogenlday) suggests that criti-cal depletion of lean tissue may occur after 14 days ofstarvation. Therefore, nutrition support should be mi-tiated in patients who are not expected to resume oral

feeding for 7 to 10 days. (C)3. Trauma patients fed by enteral nutrition have fewer

complications than those given TPN. (B) However, itis not clear whether enteral nutrition support providesa specific benefit or whether TPN itself or overfeed-ing by TPN is associated with increased infections.

4. No definitive conclusions can be made regarding the

clinical efficacy of specialized nutrient formulations

(containing to-3 fatty acids, arginine, nucleic acids,glutamine, and/or BCAAS) because of conflicting re-

sults from various studies.

1. Perform PRCTs to determine whether enteral nutrition

support affects clinical outcome in uniform groups ofcritically ill patients. These trials should be designed so

that the control group does not receive nutrition sup-port. Furthermore, these trials may need a “fall-safe”process for the control group that does not allow a “pro-longed” period ofstarvation (possibly 7 to 14 days). Theendpoints should include morbidity, mortality, organfunction, length ofintensive care unit and hospital stay,and long-term rehabilitation and quality of life.

2. Ifenteral feeding is shown to be ofbenefit, further stud-

ies should be performed to determine the optimal tim-ing and amount of enteral nutrients needed to improveoutcome.

3. Perform PRCTS to determine the clinical efficacy of in-dividuai specific nutrient supplements. The appropri-

ate control group (standard enteral formula feeding vsno feeding) will depend on results generated from thestudies comparing feeding with no feeding.

PERIOPERATIVE NUTRITION SUPPORT

A total of 33 PRCTs,’7�’77’22�254 involving over 2500 sur-

gical patients, were evaluated in this review. Only trials

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that met the following criteria were included: full-lengthpublication in an English language, peer-reviewed journal;presentation of an a priori hypothesis; nutritional therapy

was given for at least 5 days and provided sufficient cab-ries and nitrogen to meet daily requirements; and data onclinical outcome were reported. When multiple endpointswere presented, the most “clinically significant” outcomewas selected (eg, “septic episodes” in preference to “woundinfections”). If the original experimental design includedstratification, important results from stratified subgroupswere evaluated, but retrospectively identified patient sub-groups or endpoints were not. When a significant numberof similar studies were available, data were pooled to cab-culate a pooled estimate of the risk difference betweenpatients given nutrition support and the control group (rateof complication in nutritionally supported group minusrate in control group).25�

Preoperative TPN

PARENTERAL NUTRITION

Thirteen PRCTs, involving over 1250 patients, were iden-tified (Table I). Most patients in these studies had gas-trointestinal cancer and were considered by the authors

to be at least “moderately malnourished” on the basis ofweight loss, plasma proteins, or prognostic indices. Pa-tients randomized to nutrition support usually received

TPN for at least 7 to 10 days before surgery (Table I). Nineof the 13 studies found that patients who received preop-erative TPN had fewer postoperative complications thanthe control group; in five studies these differences reachedconventionally accepted statistical significance. Thepooled results indicate that TPN therapy decreased theoverall risk of postoperative complications by approxi-mately 10% (ie, a reduction in rate of complications from

approximately 40% to 30%) (Table I and Fig 1). Althoughone study found a statistically significant reduction in post-operative mortality in patients who received preoperativeTPN,23#{176}no difference between groups was demonstrated

in the pooled analysis (Table I).

Postoperative TPN

Routine administration of TPN to general surgical pa-tients in the immediate postoperative period was studiedin nine PRCTs involving over 700 patients (Table II andFigure 2). These studies mostly contained patients withgastrointestinal cancer who were considered by the au-thors to be at least “moderately malnourished” on the ba-sis of weight loss, plasma proteins, or prognostic indices.

The pooled analysis suggests that TPN therapy increasedthe overall risk ofpostoperative complications by approxi-mately 10% (ie, an increase in rate of complications fromapproximately 30% to 40%). No statistically significant dif-

ferences in mortality between groups were found.

ENTERAL NUTRITION

Preoperative Enteral Tube Feeding

Two PRCTs compared the use of preoperative enteraltube feedings with an ad libitum oral diet (Table 111)244 24�

Most of the patients studied had cancer. The incidence of

postoperative complications tended to be bower in patientswho received preoperative enterab tube feedings (overallincidence = 12%) than in the control group (overall mci-dence =30%); the difference between groups was statisti-cabby significant in one study.245 One PRCT, containing only20 patients with esophageal cancer, compared preopera-

tive enteral nutrition with TPN and found no significant

differences in postoperative complications or mortality be-tween groups.246

Postoperative Enteral Tube Feeding

Four PRCTs compared early postoperative jejunal tubefeeding with the usual advancement of an oral diet as tob-erated (Table III).247250 Most patients had gastrointestinal

cancer. The aggregate data show no obvious differencesin postoperative morbidity or mortality. The effect of post-

operative jejunostomy tube feeding with a formula en-

riched with arginine, ribonucleic acids, and w-3 fatty ac-ids was compared with a standard formula in a PRCT

involving patients with cancers of the upper gastrointesti-nal tract.25’ In an intent-to-treat analysis, no significant dif-ferences were found between groups. However, when onlypatients who were successfully fed were evaluated, thosewho received the enriched formula had fewer infectionsand wound complications and a shorter duration of hos-pitalization than those who received the standard formula.However, in this subgroup analysis, more patients withlonger lengths of stay were eliminated from the treatmentgroup than from the control group.252

The effect of supplementary tube feeding was evaluatedin elderly women after surgical repair of a femoral neck

fracture.2� Of 744 patients, 122 were “thin,” defined as 1to 2 standard deviations below the mean weight, or “very

thin,” defined as >2 standard deviations below the meanweight. These 122 women were randomized to receive ei-

ther a normal ward diet plus 1000 kcal each night bynasogastric tube or a normal ward diet alone. Women ran-domized to receive additional enterab nutrition had ashorter time until weight-bearing and independent mobil-ity and were discharged from the hospital earlier than thoserandomized to a normal diet. Furthermore, mortality ratesin the supplemented very thin patients were numerically,

although not statistically significantly, bower than in thevery thin control group (8% and 22%, respectively). Simi-

barly, Delrni et al2� found that the duration of hospitaliza-tion and the rates of both short-term and long-term (6months) complications were lower in elderly women givenoral nutritional supplementation after surgical repair of afractured femoral neck than in women who were random-ized to receive regular meals.

1. TPN given to “malnourished” (defined by weight boss,plasma proteins, or prognostic indices) patients withgastrointestinal cancer for 7 to 10 days before sur-gery decreases postoperative complications by ap-proximately 10%. (A)

2. Routine use of early postoperative TPN in “malnour-

ished” (defined by weight loss, plasma proteins, orprognostic indices) general surgical patients who do

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60 � Pre-op TPN and Morbidity -

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not receive preoperative TPN increases postopera-tive complications by approximately 10%. (A)

3. Postoperative nutrition support is necessary for pa-tients unable to eat for long periods after surgery toprevent adverse effects of starvation. The exact du-ration of starvation that can be tolerated without in-creased morbidity is unknown. The opinion of thissubcommittee is that wound healing and recoveryfrom surgery may be impaired if TPN is not startedwithin 5 to 10 days after the operation in patients who

are unable to eat or tolerate enteral feedings. (C)4. In the majority of currently published PRCTs evalu-

ating the use of perioperative TPN, the quantity andtype of substrates given were not optimal by currentstandards. For example, calories were often given inamounts substantially greater than metabolic needs.

Therefore, it is possible that outcomes in many ofthese trials would be different if the trials were re-peated using our present-day understanding of caloricneeds and other metabolic requirements in specific

patient groups. (C)5. Postoperative enteral feeding given to underweight

elderly women after surgery for hip fracture speedsrecovery of mobility, decreases postoperative corn-plications, and decreases the length of hospital stay.(A)

1. Further studies are needed to help identify specificsubsets of patients who may benefit from preopera-tive TPN. These studies should also consider long-term outcomes and include a cost-benefit analysis ofnutritional therapy.

2. PRCTs are needed to evaluate the clinical efficacy ofpreoperative enteral feeding in patients consideredto be at high risk for postoperative complications.

3. Evaluate the potential clinical benefits of specific nu-trients, such as arginine, glutamine, nucleotides and

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nucleosides, w-3 fatty acids, and antioxidants, in en-hancing immune function, ameliorating the inflamma-

tory response, and enhancing recovery from surgery.

CONCLUDING REMARKS

The development of modern nutrition support has beenhailed as one of the major advances in patient care in this

century. To continue to improve the nutritional manage-ment ofpatients, it is important to have a clear understand-ing of the published data evaluating the use of nutritionsupport and to target areas that deserve future investiga-tion. This document represents a careful review ofthe iden-tified published literature evaluating nutritional assess-ment and the clinical efficacy of enterab and parenteralnutrition. The interpretation of data presented here doesnot always reflect uniformity of opinion among all mern-bers of each subcommittee but does represent a consen-sus of the entire group.

The applicability of data obtained from published clini-cal trials to current practice is limited because of short-comings in study design and the absence of studies ad-dressing some important clinical issues. In addition,changes that have occurred in both medical and nutritionaltherapy may limit the application ofdata from earlier clini-cal trials to current practice. Therefore, practice guide-lines for nutrition support cannot be based solely on thisreport. Indeed, more than half of the A.S.P.E.N. Guide-lines2� and the Georgetown University School of MedicineConference practice guidelines for TPN257 are based onexpert opinion rather than research-based evidence. Nev-ertheless, this document should serve to inform the prac-titioner of the existing literature within the five areas re-viewed by this conference. This document also serves asa challenge to obtain the objective evidence needed todetermine the most clinically effective and cost-effectiveuse of nutritional therapy.

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ACKNOWLEDGMENT

This conference received educational grants from thefollowing: Clintec Nutrition, McGaw Inc, Mead Johnson

Nutritional Groups, Ross Laboratories, and The AmericanDietetic Association.

REFERENCES

1. Butterworth CE: Skeleton in the hospital closet. Nutrition Today9:4, 1976

2. Bistrian BR, Blackburn GL, Vitale J, et al: Prevalence of malnutri-tion in general medical patients. JAMA 235: 1567, 1976

3. Bistrian BR, Blackburn GL, Hallowell E, et al: Protein status of gen-eral surgical patients. JAMA 230:858, 1974

4. Hill GL, Blackett RL, Pickford I, et al: Malnutrition in surgical pa-tients; an unrecognized problem. Lancet 1:689, 1977

5. Weinsier RL, Humber EM, Krumdieck CL, et al: Hospital malnutri-

tion: a prospective evaluation of general medical patients during thecourse of hospitalization. Am J Clin Nutr 32:418, 1979

6. DeWys WD, Begg C, Lavin PT, et al: Prognostic effect of weight lossprior to chemotherapy in cancer patients. Am J Med 69:491, 1980

7. Morgan DB, Hill GL. Burkinshaw L: The assessment of weight loss

from a single measurement of body weight: The problems and limi-tations. Am J Clin Nutr 33:2101, 1980

8. Jelliffe DB: The assessment of the nutritional status of the commu-nity: With special reference to field surveys in developing regions ofthe world. Geneva� World Health Organization, 1966

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80 Post-Op TPN and Morbidity

Randomized Controlled Trials

60

1

I

117 47 300 122 56

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-60

N= 44

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726

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TABLE IIIResults ofprospective randomized controlled trials evaluating perioperative enteral nutritional therapy

Ref First Author(reference)

Patient.

PopulationNutritional

TherapyNumber of

.Patients

Corn

EN

Majorphcat,ons

(%�

Control

PostoperativeMortality

(%�

EN Control

C omments

Preoperative Enteral Nutrition:

244 von Meyenfeldt Gastric,Colorectal CA

10 d oratiNG feeding 101 12 14 8 4 Another group receivedpreop TPN

245 Shukia GI, breast, andoropharynx

CA andbenign disease

10 d NG feeding 1 10 10 37* 6 12 40-50% of EN group

had tube feedingcomplications

Postoperative Enteral Nutrition:

247 Sagar GI CA 5 d NJ feeding 30 20 33 NR NR Signif. shorter lengthofstay in EN group

248 Ryan Colorectal CA 10 d NCJ feeding 14 0 43 NR NR

249 Smith GI CA 10 d NCJ feeding 50 44 36 17 4 Signif. longer lengthof stay in EN group

250 lovinelli Oropharynx CA >5 d NJ feeding 48 15 22 NR NR

CA = cancer; EN = enteral nutrition; NJ = nasojejunal tube; N�J = needle catheterjejunostomy tube; NG = nasogastric tube; ND nasoduodenal

tube; NH = not reported. * Value significantly different from EN group, p < .05.

0b 40

0

�20

= 0

(I,

-20

Figure 2. Prospective randomized controlled trials evaluating the effect of early postoperative TPN (without preoperative TPN) on postoperativecomplications. The mean increase or decrease in postoperative complications with 95% confidence intervals are shown for each study. Values above0 indicate a decrease in complications associated with the use of TPN while those below 0 indicate an increase in complications. When the 95%

confidence intervals are above or below 0 the differences in postoperative complications between the group receiving TPN and the control group arestatistically significant. The pooled analysis of these trials found a 10% increase (an overall increase from 30% to 40%) in postoperative complications

in patients who received postoperative TPN.

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9. Frisancho AR: New norms of upper limb fat and muscle areas for

assessment of nutritional status. Am J Clin Nutr 34:2540, 198110. Harries AD, Jones LA, Heatley RV, et al: Malnutrition in inflamma-

tory bowel disease: An anthropometric study. Human Nutrition Clini-cal Nutrition 36C:307, 1982

1 1. Thuluvath PJ, Thger DR: How valid are our reference standards ofnutrition? Nutrition 11:731, 1995

12. Hall JCH, O’Quigley J, Giles GR, et al: Upper limb anthropometry:The value of measurement variance studies. Am J Clin Nutr 33:1846,1980

13. Forbes GF, Bruinmg GJ: Urinary creatinine excretion and lean bodymass. Am J Clin Nutr 29: 1359, 1976

14. Reinhardt GE Myscofski JW, Wilkens DB, et al: Incidence and mor-tality of hypoalbuminemic patients in hospitalized veterans. JPEN4:357, 1980

15. Anderson CF, Wochos DN: The utility of serum albumin values inthe nutritional assessment of hospitalized patients. Mayo Clin Proc57:181, 1982

16. Apelgren KN, Rombeau JL, Twomey PL, et al: Comparison of nutri-tional indices and outcome in critically ill patients. Crit Care Med10:305, 1982

17. Klein S: The myth of serum albumin as a measure of nutritionalstatus. Gastroenterology 99: 1845, 1990

18. Gray GE, Meguid MM: Can total parenteral nutrition reverse hypoal-buminemia in oncology patients? Nutrition 6:225, 1990

19. Broom J, F’raser MH, McKenzie K, et al: The protein metabolic re-sponse to short-term starvation in man. Clin Nutr 5:63, 1986

20. Keys A, Brozek J, Henschel A, et al (eds): The biology of humanstarvation. Minneapolis: University of Minnesota Press, 1950

21. Halmi KA, Struss AL, Owen WP, et al: Plasma and erythrocyte aminoacid concentrations in anorexia nervosa. JPEN 1 1:458, 1987

22. Castenada C, Charnley JM, Evans WJ, et al: Elderly womenaccomodate to a low-protein diet with losses of body cell mass,muscle function, and immune response. Am J Clin Nutr 62:30, 1995

23. Kelleher PC, Phinney SD, Sims EAH, et al: Effects of carbohydrate-

containing and carbohydrate-restricted hypocaloric and eucaloricdiets on serum concentrations of retinol-binding protein, thyrox-

me-binding prealbumin and transferrin. Metabolism 32:95, 198324. Hedlund JU, Hansson LO, Ortqvist AB: Hypoalbumineniia in hospi�

talized patients with community-acquired pneumonia. Arch Intern

Med 155:1438, 199525. Nieken J, Mulder NH, Buter J, et al: Recombinant human interleukin-

6 induces a rapid and reversible anemia in cancer patients. Blood86:900, 1995

26. O’Riordain MG, Ross JA, Fearon KC, et al: Insulin andcounterregulatory hormones influence acute-phase protein produc-tion in human hepatocytes. Am J Physiol 269:E323, 1995

27. Cano N, Costanzo-DufetelJ, CalaiR, et al: Pre-albumin retinol-bind-ing protein-retmolcomplex in hemodialysis patients. Am J Clin Nutr47:664, 1988

28. Buzby GP, Mullen JP, Matthews DC: Prognostic nutritional index ingastrointestinal surgery. Am J Surg 139:160, 1980

29. Harvey KB, Moldawer LL, Bistrian BR, et al: Biological measures

for the formulation of a hospital prognostic index. Am J Clin Nutr34:2013, 1981

30. Baker JP, Detsky AS, Wesson DE, et al: Nutritional assessment: Acomparison ofclmicaljudgment and objective measurements. N EnglJ Med 306:969, 1982

31. Detsky AS, McLaughlin JR, BakerJP, et al: What is subjective globalassessment of nutritional status? JPEN 1 1:8, 1987

32. Pikul J, Sharpe MD, Lowndes R, et al: Degree of preoperative mal-nutrition is predictive of postoperative morbidity and mortality in

liver transplant recipients. Transplantation 57:469-472, 199433. Enia G, Sicuso C, Alati G, et al: Subjective global assessment of nu

trition in dialysis patients. NephrolDial Transplant 8:1094-1098, 199334. Detsky AS, Baker JP, Mendelson RA, et al: Evaluating the accuracy

ofnutntional assessment techniques applied to hospitalized patients:Methodology and comparisons. JPEN 8:153, 1984

35. Russell D, Leiter LA, WhitwellJ, et al: Skeletal muscle function dur-

ing hypocaloric diets and fasting: a comparison with standard nutri-tional assessment parameters. Am J Clin Nutr 37: 133, 1983

36. Zeiderman MR, McMahon MJ: The role of objective measurementof skeletal muscle function in the pre-operative patient. Clin Nutr8:161, 1989

37. Windsor JA, Hill GL: Weight loss with physiologic impairment: A

basic indicator of surgical risk. Ann Surg 207:290, 198838. Hamill PVV: NCHS growth curves for children, birth to 18 years.

Washington, DC: (Publication No. IPHSI 78-1650) National Centerfor Health Statistics, US Department of Health, Education, and Wel-fare, 1977

39. Ramsey B, Farrell P, Pencharz P, et al: Nutritional assessment and

management in cystic fibrosis: A consensus report. Am J Clin Nutr

55:108-116, 1992

40. Sazawal S, Black R, Bhan MN, et al: Zinc supplementation in young

children with acute diarrhea in India. N Engl J Med 333:839-844,

1995

41. Shepherd RW, Holt TL, Thomas RI, et al: Controlled studies of ef-

fects on nutritional growth retardation, body protein turnover, andcourse of pulmonary disease. J Pediatr 109:788-794, 1986

42. Dalzell AM, Shepherd RW, Dean B, et al: Nutritional rehabilitationof cystic fibrosis: A 5-year follow-up study. J Pediatr GastroenterolNutr 15:141-145, 1992

43. Steinkamp G, von der Hardt H: Improvement of nutritional status

and lung function after long-term nocturnal ga.strostomy feedings incystic fibrosis. J Pediatr 124:244-249, 1994

44. Cunningham J: Body composition and nutrition support in pediat-

tics: What to defend and how soon to begin. Nutr Clin Pract 10:177-182, 1995

45. Nightingale JMD, Lennard-Jones JE, Walker ER, et al: Jejunal effluxin short bowel syndrome. Lancet 336:765, 1990

46. Gouttebel MC, Saint-Aubert B, Astre C, et al: Total parenteral nutri-

tion needs in different types of short bowel syndrome. Dig Dis Sci31:718, 1986

47. Fleming CR: Comprehensive care of the gut failure patient: Presentand future. Trans Am Climat Assoc 98: 197-207, 1986

48. Howard L, Ament M, Fleming CR, et al: Current use and clinicaloutcome of home parenteral and enteral nutrition therapies in the

United States. Gastroenterology 109:355-365, 1995

49. Cosnes J, Gendre JP, Evard D, et al: Compensatory enteralhyperalimentation for management of patients with severe shortbowel syndrome. Am J Clin Nutr 41:1002, 1985

50. Heymsfield SB, Smith-AndrewsJL, Hersh T: Home nasoenteric feed-

ing for malabsorption and weight loss refractory to conventionaltherapy. Ann Intern Med 98:168, 1983

51. Lennard-Jones JE: Oral rehydration solutions in short bowel syn-

drome. Clin Ther 12(Suppl A):129, 1990

52. Griffiths AM, Ohlsson A, Sherman PM, et al: Meta-analysis of en-teral nutrition as a primary treatirient of active crohn’s disease. Gas-troenterology 108: 1056-1067, 1995

53. Trallori MA, D’Albasio GD, Milla M, et al: Defined-formula diets ver-

sus steroids in the treatment of active Crohn’s disease. Scand JGastroenterol 31:267-272, 1996

54. Fernandez-Banares F. Cabre E, Esteve-Comas M, et al: How effec-

tive is enteral nutrition in inducing clinical remission in active Crohn’s

disease? A meta-analysis of the randomized clinical trials. JPEN19:356-364, 1995

55. Summers RW, Switz i)M, Sessions JT Jr, et al: National cooperativeCrohn’s disease study: Results of drug treatment. Gastroenterology77:847-869, 1979

56. Meyers S, Janowitz 1-ID: “Natural history” ofCrohn’s disease. An ana-lytic review of the placebo lesson. Gastroenterology 87:1189-1192,

1984

57. Wright RA, Adler EC: Peripheral parenteral nutrition is no betterthan enteral nutrition in acute exacerbation of Crohn’s disease: Aprospective trial. J Clin Gastroenterol 12:396-399, 1990

58. Lochs H: Has total bowel rest been a beneficial effect in the treat-ment of Crohn’s disease? Clin Nutr 2:61-64, 1983

59. Greenberg GR, Fleming CR, Jeejeebhoy KN et al: Control trial ofbowel rest and nutritional support in the management of Crohn’sdisease. Gut 29:1309-1315, 1988

60. Dickinson EU, Ashton MG, et al: Controlled trial of intravenous

hyperalimentation and total bowel rest as an adjunct to the routinetherapy of acute colitis. Gastroenterology 79:1199-1204, 1980

61. McIntyre PB, Powell-TuckJ, Wood SR, et al: Controlled trial of bowel

rest in the treatment of severe acute colitis. Gut 27:481-485, 198662. Gonzalez-Huix F, Fernandez-Banares F� Esteve-Comas M, et al: En-

teral versus parenteral nutrition as adjunct therapy in acute ulcer-ative colitis. Am J Gastroenterol 88:227-232, 1993

63. Belluzzi A, Brignola C, Campieri M, et al: Effect ofan enteric-coatedfish-oil preparation on relapses in Crohn’s (lisease. N Eng J Med334:1557-1560, 1996

64. Lorenz-Meyer H, Bauer P, Nicolay C, et al: Omega-3 fatty acids andlow carbohydrate diet for maintenance of remission in Crohn’s dis-

ease. Scand J Gastroenterol 31:778-785, 1996

Dow



arch 2022


65. Aslan A, Thdafilopoulos G: Fish oil fatty acid supplementation inactive ulcerative colitis: A double-blind, placebo-controlled, cross-over study. Am J Gastroenterol 87:432-437, 1992

66. Lorenz R, Weber PC, Szimnau P, et al: Supplementation with n-3 fattyacids from fish oil in chronic inflammatory bowel disease-a ran-domized, placebo-controlled, double-blind cross-over trial. J InternMed 225:225-232, 1989

67. Hawthorne AB, Daneshmend TK, Hawkey CJ, et al: Treatment ofulcerative colitis with fish oil supplementation: A prospective 12month randomized controlled trial. Gut 33:922-928, 1992

68. Stenson WF, Cort D, Rodgers J, et al: Dietary supplementation withfish oils in ulcerative colitis. Ann Intern Med 116:609-614, 1992

69. Koeschke K, Ueberschaer B, Pietsch A, et al: n-3 fatty acids onlydelay early relapse of ulcerative colitis in remission. Dig Dis Sci41:2087-2094, 1996

70. Weschmeyer P, Pemberton JH, Phillips SF: Chronic pouchitis afterileal pouch-anal anastomosis: Responses to butyrate and glutamine

suppositories in a pilot study. Mayo Clin Proc 68:978-981, 1993

71. Edmunds LH Jr, Williams GM, Welch CE: External fistulas arisingfrom the gastrointestinal tract. Ann Surg 152:445, 1960

72. Himal HS, Allard JR, Nadeau JE, et al: The importance of adequate

nutrition in closure ofsmall intestinal fistulas. BrJ Surg 61:724, 197473. DiCostanzo J, Cano N, Martin J, et al: Treatment of external gas-

trointestinal fistulas by a combination of total parenteral nutrition

and somatost.atin. JPEN 11:465, 198774. Greenberg GR: Inflammatory bowel disease. In: Nutrition and me-

tabolism in patient care, Kinney J, Jeejeebhoy KN, Hill G, Owen 0

(eds). WE Saunders, 1988, p 27275. Kelts DG, Grand RJ, Davis-Kraft L, et al: Nutritional basis of growth

failure in children and adolescents with Crohn’s disease. Gastroen-terology 76:720-727, 1978

76. Polk DB, HattnerJT, KernerJA Improved growth and disease activ-ity after intermittent administration ofa defmed formula diet in chil-

dren with Crohn’s disease. JPEN 16:499-504, 199277. Kirschner BS, Klich JR, Kalman 55, et al: Reversal of growth retar-

dation in Crohn’s disease with therapy emphasizing oral nutritionalrestitution. Gastroenterology 80:10-15, 1981

78. Aiges H, Markowita J, Rosa J, et al: Home nocturnal supplemental

nasogastric feedings in growth-retarded adolescents with Crohn’sdisease. Gastroenterology 97:905-910, 1989

79. Sanderson IR, Udeen 5, Davies PSW, et al: Remission induced by anelemental diet in small bowelCrohn’sdisease. Arch Dis Child 61:123-127, 1987

80. Belli DC, Seidman E, Bouthiller L: Chronic intermittent elementaldiet improves growth failure in children with Crohn’s disease. Gas-

troenterology 94:603-610, 198881. Klein E, Shinebaum 5, Ben-Mi G, et al: Effects of total parenteral

nutrition on exocrine pancreatic secretion. Am J Gastroenterol78:31-33, 1983

82. Johnson LR, Schanbachter LM, Dudrick SI, et al: Effect of long-term

parenteral feeding on pancreatic secretion and serum secretin. AmerJ Physiol 233:E524-E529, 1977

83. Grant JP, James 5, Grabowski V, et al: Total parenteral nutrition in

pancreatic disease. Ann Surg 200:627-631, 198484. Grundfest 5, Steiger E, Selinkoff P, et al: The effect of intravenous

fat emuisions in patients with pancreatic fistula. JPEN 4:27, 198085. Bivins BA, Bell RM, Rapp RP, et al: Pancreatic exocrine response to

parenteral nutrition. JPEN 8:34, 198486. Edelman K, ValenzuelaJE: Effect ofmtravenous lipid on human pan-

creatic secretion. Gastroenterology 85: 1063, 198387. Variyam EP, Fuller RK, Brown FM, et al: Effect ofparenteral amino

acid on human pancreatic exocrine secretion. Dig Dis Sci 30:541,1980

88. Silberman H, Dixon NP, Eisenberg D: The safety and efficacy of alipid-based system of parenteral nutrition in acute pancreatitis. AmJ Gastroenterol 77:494-497, 1977

89. Leibowitz AB, O’Sullivan P, Iberti TJ: Intravenous fat emulsions andthe pancreas: A review. Mt Sinai J Med (NY) 59:38-42, 1992

90. NoseworthyJ, Colodny MI, Eraklis AJ: Pancreatitis and intravenousfat: An association in patients with inflammatory bowel disease. JPediatr Surg 18:269, 1983

91. Buckspan R, Woltering E, Waterhouse G: Pancreatitis induced byintravenous fat emulsion in an alcoholic patient. South MedJ 77:252,

1984

92. Lashner BA, Kirsner JB, Hanauer SB: Acute pancreatitis associatedwith high-concentration lipid emulsion during total parenteral nu-

trition therapy for Crohn’s disease. Gastroenterology 90:1039, 1986

93. Ragins H, Levenson SM, Singer R, et al: Intrajejunal administration

of an elemental diet at neutral pH avoids pancreatic stimulation.Am J Surg 126:606, 1973

94. Grant JP, Davey-McCrae J, Snyder PJ: Effect of enteral nutrition on

human pancreatic secretions. JPEN 1 1:302-304, 198795. Keith RG: Effect of a low fat elemental diet on pancreatic secretion

during pancreatitis. Surg Gynecol Obstet 151:337, 198096. DiMagno EP, Vay LW, Summerskill HJ: Intraluminal and

postabsorptive effects of amino acids on pancreatic enzyme secre-tion. J Lab Clin Med 82:241-248, 1971

97. Vidon N, Hecketsweiler P, ButelJ, et al: Effect of continuous jejunalperfusion of elemental and complex nutritional solutions on pan-

creatic enzyme secretion in human subjects. Gut 19: 194, 1978

98. Ertan A, Brooks FF, Ostrow D, et al: Effect ofjejunal amino acidperfusion and exogenous cholecystokinin on the exocrine pancre-

atic and biliary secretions in man. Gastroenterology 61:686, 197199. Bradley EL: A clinically based classification system for acute pan-

creatitis. Arch Surg 128:586-590, 1993100. Uomo G, Rabitti PC, Laccetti M, et al: Predictive evaluation of acute

necrotizing pancreatitis: Results of a prospective study. PresseMedicale 24:263-266, 1995

101. Sax HC, Warner BW, Talamini MA, et al: Early total parenteral nutri-tion in acute pancreatitis: Lack of beneficial effects. Am J Surg

153:117-124, 1987

102. McClave SA, Greene LM, Snider HL, et al: Comparison ofthe safetyof early enteral vs parenteral nutrition in mild acute pancreatitis.

JPEN 21:14-20, 1997

103. Dickerson RN, Vehe KL, Mullen JL, et al: Resting energy expendi-ture in patients with pancreatitis. Crit Care Med 19:484-490, 1991

104. Shaw JH, Wolfe RR: Glucose, fatty acid, and urea kinetics in pa-tients with severe pancreatitis. The response to substrate infusion

and total parenteral nutrition. Ann Surg 204:665, 1986105. Sitzmann JV, Stemborn PA, Zinner MJ, et al: Total parenteral nutri-

tion and alternate energy substrates in treatment of acute pancre-atitis. Surg Gynecol Obstet 168:31 1-317, 1989

106. Goodgame JT, Fischer JE: Parenteral nutrition in the treatment of

acute pancreatitis. Ann Surg 186:651-658, 1977107. Feller JH, Brown RA, Toussaint GPM, et al: Changing methods in

the treatment of severe pancreatitis. Am J Surg 127:196-201, 1974108. Kalfarentzos FE, Karavias DD, Karatzas TM, et al: Total parenteral

nutrition in severe acute pancreatitis. J Am Coll Nutr 10:156-162,1991

109. Robin Al:), Campbell R, Palani C, et al: Total parenteral nutrition dur-

ing acute pancreatitis: Clinical experience with 156 patients. WorldJ Surg 14:572-579, 1990

110. Blackburn GL, Williams LF, Bistrian BR, et al: New approaches to

the management of severe acute pancreatitis. Am J Surg 131:114-

124, 19761 1 1. Frey CF: Classification of acute pancreatitis. mt J Pancreatology

9:39-49, 1991

112. Kudsk KA, Campbell SM, O’Brien T, et al: Postoperative jejunalfeedings following complicated pancreatitis. Nutr Clin Pract 5:14-

17, 19901 13. Voitk A, Brown RA, Echave V, et a!: Use of an elemental diet in the

treatment ofcomplicated pancreatitis. Am J Surg 125:223-227, 19731 14. Pederzoli P, Bassi C, Falconi M, et al: Conservative treatment of ex-

ternal pancreatic fistulas with parenteral nutrition alone or in corn-bination with continuous intravenous infusion of somatostatin, glu-cagon, or calcitonin. Surg Gynecol Obstet 163:428-431, 1986

115. Vanyam EP: Central vein hyperalimentation in pancreatic ascites.Am J Gastroenterol 78:178-181, 1983

116. Mendenhall C, Bongiovanni G, Goldberg 5, et al: VAcooperative study

on alcoholic hepatitis. III: Changes in protein-calorie malnutritionassociated with 30 days of hospitalization with and without enteralnutritional therapy. JPEN 9:590-596, 1985

1 17. McCullough AJ, Mullen KD, Smanik E.J, et al: Nutritional therapyand liver disease. Gastroenterol Clin North Am 18:619-643, 1989

1 18. Bonkovsky HL, Fiellin DA, Smith DA, et al: A randomized, controlledtrial oftreatment ofalcoholic hepatitis with parenteral nutrition andoxandrolone. I. short-term effects on liver function. Am JGastroenterol 86: 1200-1208, 1991

1 19. Bonkovsky HL, Singh RH, Jafri Ill, et al: A randomized, controlledtrial oftreatment ofalcoholic hepatitis with parenteral nutrition and

oxandrolone. II. short-term effects on nitrogen metabolism, mets-bolic balance, and nutrition. Am J Gastroenterol86:1209-1218, 1991

120. Mendenhall CL, Mortitz TE, Roselle GA, et al: A study of oral nutri-tion support with oxandrolone in malnourished patients with alco-

Dow



arch 2022


holic hepatitis: Results of a Department of Veterans Affairs coop-erative study. Hepatology 17:564-576, 1993

121. Kearns PJ, Young H, Garcia G, et al: Accelerated improvement ofalcoholic liver disease with enteral nutrition. Gastroenterology

102:200-205, 1992

122. Hirsch 5, Bunout D, de la Maza R, et al: Controlled trial on nutritionsupplementation in outpatients with symptomatic alcoholic cirrho-sis. JPEN 17:119-124, 1993

123. Naveau 5, Pelletier G, Poynard T, et al: A randomized clinical trial ofsupplementary parenteral nutrition in jaundiced alcoholic cirrhoticpatients. Hepatology 6:270-274, 1986

124. Cabre E, Gonzalez-Huix FG, Abad-Lacruz A, et al: Effect of totalenteral nutrition on the short-term outcome of severely malnour-ished cirrhotics. Gastroenterology 98:715-720, 1990

125. Naylor CD, O’Rourke K, Detsky AS, et al: Parenteral nutrition withbranched-chain amino acids in hepatic encephalopathy. A mets-

analysis. Gastroenterology 97:1033-1042, 1989

126. Marsano L, McClain Cl: Nutrition and alcoholic liver disease. JPEN15:337-344, 1991

127. Watkins JB, Glassman MS: Acute and chronic liver disease in chil-dren, IN Nutrition in pediatrics, Walker A, Watkins J (eds). Little

Brown & Co, Bostonfforonto, 1985, pp 485-497

128. Greene HE, Ghishan F: Inborn errors of metabolism that lead topermanent liver injury, IN Hepatology, Zakim D, Boyer TD (eds).WB Saunders, Philadelphia, 1982, pp 1084-1137

129. Kotler DP, Wang J, Pierson RN Jr: Body composition studies in pa-tients with the acquired immunodeficiencysyndrome. AmJ Clin Nutr42:1255-1265, 1985

130. Kotler DP, Tierney AR, Wang J, et al: Magnitude of body-cell-massdepletion and the time of death from wasting in AIDS. Am J ClinNutr 50:444-447, 1989

131. Suttmann U, Ockenga J, Selberg 0, et al: Incidence and prognosticvalue of malnutrition and wasting in human imrnunodeficiency vi-rus-infected outpatients. J Acquir Immune Defic Syndr HumRetrovirol 8:239-246, 1995

132. Palemcek JT� Graham NM, He YD, et al: Weight loss prior to clinicalAIDS as a predictor of survival. Multicenter AIDS cohort study in-vestigators. J Acquir Immune Defic Syndr Hum Retrovirol 10:366-

373, 1995

133. Keys A, Brozek J, Henschel A, et al (eds). The biology of starvation.

Minneapolis: University of Minnesota Press, 1950

134. Shike M, Russell DM, Detsky AS, et al: Changes in body composi-tion in patients with small cell lung cancer: The effect of total

parenteral nutrition as an adjunct to chemotherapy. Ann Intern Med101:303-309, 1984

135. Klein 5, Koretz RL: Nutrition support in patients with cancer Whatdo the data really show? Nutr Clin Pract 9:91-100, 1994

136. Klein 5, Simes J, Blackburn GL: Total parenteral nutrition and can-

cer clinical trials. Cancer 58:1378-1386, 1986137. McGeer AJ, Detsky AS, O’Rourke KO: Parenteral nutrition in cancer

patients undergoing chemotherapy: Ameta-analysis. Nutrition 6:233-240, 1990

138. Jebb SA, Osborne RJ, Maughan TS, et al. S-Fluorouracil and folinic

acid-induced mucositis: no effect of oral glutamine supplements-tion. Br J Cancer 70:732-735, 1995

139. Weisdorf SA, Lysne J, Wind D, et al: Positive effect of prophylactictotal parenteral nutrition on long-term outcome of bone marrowtransplantation. Transplantation 43:833-838, 1987

140. Szeluga DJ, Stuart RK, Brookmeyer R, et al: Nutritional support ofbone marrow transplant recipients: A prospective randomized cmi-cal trial comparing total parenteral nutrition to an enteral feedingprogram. Cancer Res 47:3309-3316, 1987

141. Ziegler TR, Young LS, Benfell K, et al: Clinical and metabolic effi-cacy of glutamine-supplemented parenteral nutrition after bone

marrow transplantation. Ann Intern Med 116:821-828, 1992

142. Schloerb PR, Amare M: Total parenteral nutrition with glutamine inbone marrow transplantation and other clinical applications (A ran-domized double-blind study). JPEN 17:407-413, 1993

143. Singer P, Rothkopf MM, Kvetan V, et al: Risks and benefits of homeparenteral nutrition in the acquired immunodeficiency syndrome.

JPEN 15:75-79, 1991144. Brolin RE, Gorman RC, Milgrim LM, et al: Use of nutrition support

in patients with AIDS: A four-year retrospective review. Nutrition7:19-22, 1991

145. McKinley MJ, Goodman-Block J, Lesser ML, et al: Improved bodyweight status as a result of nutrition intervention in adult, HIV posi-tive outpatients. J Am Diet Assoc 94:1014-1017, 1994

146. Burger B, Ollenschlager G, Schrappe M, et al: Nutrition behavior ofmalnourished HIV ubfected patients and intensified oral nutritionintervention. Nutrition 9:43-44, 1993

147. Chlebowski RT, Grosvenor M, Lillington L, et al: Dietary intake andcounseling, weight maintenance, and the course of HIV infection. J

Am Diet Assoc 95:428-432, 1995148. Kotler DP, Tierney AR, Culpepper-Morgan JA, et al: Effect of home

total parenteral nutrition on body composition in patients with ac-quired immunodeficiency syndrome. JPEN 14:454-458, 1990

149. Kotler DP, Tierney AR, Ferraro R, et al: Enteral alimentation andrepletion ofbody cell mass in malnourished patients with acquired

immunodeficiency syndrome. Am J Clin Nutr 53:149-154, 1991

150. Stack JA, Bell SJ, Burke PA, et al: High-energy, high-protein, oral,liquid, nutrition supplementation in patients with HIV infection: Ef-fect on weight status in reltion to incidence of secondary infection.

J Am Diet Assoc 96:337-341, 1996

151. Chlebowski RT, Beall G, Grosvenor M, et al: Long-term effects ofearly nutritional support with new enterotropic peptide-based for-

mula vs standard enteral formula in HIV-infected patients: Random-ized prospective trial. Nutrition 9:507-512, 1993

152. Suttmann U, OckengaJ, Schneider H, et al: Weight gain and increasedconcentrations of receptor proteins for tumor necrosis factor after

patients with symptomatic HIV infection received fortified nutritionsupport. J Am Diet Assoc 96:565-569, 1996

153. Hellerstein MK, Wu K, McGrath M, et a]: Effects of dietary n-3 fatty

acid supplementation in men with weight loss associated with theacquired immune deficiency syndrome: Relation to indices of

cytokine production. J Acquir Immune Defic Syndr Hum Retrovirol11:258-270, 1996

154. Bell SI, Chavali 5, Bistrian BR, et al: Dietary fish oil and cytokineand eicosanoid production during human immunodeficiency virus

infection. JPEN 20:43-49, 1996

155. Rickard KA, et al: Effectiveness of enteral and parenteral nutritionon the nutritional management of children with Wilms’ tumors. AmJ Clin Nutr 33:2622-2629, 1980

156. Carter P, et al: Nutritional parameters in children with cancer. J AmDiet Assoc 82:616-622, 1989

157. Donaldson 55, Wesley M, DeWys W, et al: A study of the nutritionalstatus of pediatric cancer patients. Am J Dis Child 135:1107-1112,

1981158. Donaldson 5, Wesley M, Ghavimi F, et al: A prospective randomized

clinical trial of total parenteral nutrition in children with cancer.Med Pediatr Oncol 10: 129-139, 1982

159. Rickard KA, Corcoran-Becker M, Loghman, et al: Effectiveness oftwo methods of parenteral nutrition support in improving musclemass of children with neuroblastorna or Wilrn’s tumor. Cancer

64:116-125, 1989

160. Ghavimi F, Sinis M, Scot B, et al: Comparison of morbidity in chil-

dren requiring abdominal radiation and chemotherapy, with and with-

out total parenteral nutrition. J Pediatr 101:530-537, 1982161. Henderson RA. Effect ofenteral tube feeding on growth of children

with symptomatic human immunodeficiency virus infection. J

Pediatr Gastroenterol 18:429, 1994

162. Miller T, Awnetwant E, Evans 5, et al: Gastrostomy tube supplemen-tation for HIV-infected children. Pediatrics 96:696, 1995

163. Howard L, Ament M, Fleming CR, et al: Current use and clinicaloutcome of home parenteral and enteral nutrition therapies in theUnited States. Gastroenterology 109:355, 1995

164. Melchior JC, Chastang C, Gelas P, et al: Efficacy of 2-month total

parenteral nutrition in AIDS patients: A controlled randomized pro-spective trial. AIDS 10:379-384, 1996

165. O’Dwyer TP, Gullane PJ, Awerbuch D, et al: Percutaneous feedinggastrostomy in patients with head and neck tumors: A 5-year re-

view. Laryngoscope 100:29-32, 1990166. Saunders JR Jr, Brown MS, Hirata RM, et al: Percutaneous endo-

scopic gastrostomy in patients with head and neck malignancies.

Am J Surg 162:381-383, 1991

167. Shike M, Berner YN, Gerdes H, et al: Percutaneous endoscopic gas-trostorny andjejunostomy for long-term feeding in patients with can-

cer ofthe head and neck. Otolaryngol Head Neck Surg 101:549-554,1989

168. Ockenga J, Suttmann U, Selberg 0, et al: Percutaneous endoscopic

gastrostomy in AIDS and control patients: Risks and other outcomes.Am J Gastroenterol 91:1817-1822, 1996

169. Moore EE, Jones TN: Benefits of immediate jejunostomy feedingafter major abdominal trauma-A prospective, randomized study. JTrauma 26:874-881, 1986

Dow



arch 2022


170. Eyer SD, Micon LT, Konstantinides FN, et al: Early enteral feedingdoes not attenuate metabolic response after blunt trauma. J Trauma34:639-643, 1993

171. Adams 5, Dellinger EP, Wertz MJ, et al: Enteral versus parenteralnutritional support following laparotomy for trauma A randomizedprospective trial. J Trauma 26:882-890, 1986

172. Moore FA, Moore EE, Jones TN, et al: TEN versus TPN followingmajor abdominal trauma-Reduced septic morbidity. J Trauma

29:916-923, 1989173. Kudsk KA, Croce MA, Fabian TC, et al: Enteral versus parenteral

feeding. Effects on septic morbidity after blunt and penetrating ab-dominal trauma Ann Surg 215:503-51 1, 1992

174. Moore FA, Feliciano DV, Andrassy RJ, et al: Early enteral feeding,

compared with parenteral, reduces postoperative septic complica-

tions. The results of a mets-analysis. Ann Surg 216:172-183, 1992

175. VA TPN Cooperative Study: Perioperative total parenteral nutritionin surgical patients. N EngI J Med 325:525-532, 1991

176. Brennan M, Pisters PW, Posner M, et al: A prospective randomized

trial of total parenteral nutrition after major pancreatic resectionfor malignancy. Ann Surg 220:436-41, 1994

177. Sandstrom R, Drott C, Hyltander A, et al: The effect of postopera-

tive intravenous feeding (TPN) on outcome following major surgeryevaluated in a randomized study. Ann Surg 217:185-95, 1993

178. Van Way CW III, Moore EE, Allo M, et al: Comparison of totalparenteral nutrition with 25 percent and 45 percent branched chain

amino acids in stressed patients. Am Surg 51:609-616, 1985179. OkadaA, Mon 5, Totsuka M, et al: Branched-chain amino acids mets-

bolic support in surgical patients: A randomized, controlled trial inpatients with subtotal or total gastrectomy in 16 Japanese institu-tions. JPEN 12:332-337, 1988

180. Jaing Z, Zhang F, Zhu Y, et al: Evaluation of parenteral nutrition inthe postoperative patient. Surg Gynecol Obstet 166:1 15-120, 1988

181. Cerra FE, Upson D, Angelico R, et al: Branched chains support post-

operative protein synthesis. Surgery 92:192-199, 1982

182. Cerra FE, MazuskiJE, Chute E, et al: Branched chain metabolic sup-

port. Aprospective, randomized, double-blind trial in surgical stress.Ann Surg 199:286-291, 1984

183. Rowlands B, Hunt D, Roughneen P, et al: Intravenous and enteral

nutrition with branched chain amino acid enriched products follow-ing multiple trauma with closed head injury. JPEN 10:45, 1986

184. Foley EF, Borlase BC, Dzik WH, et al: Albumin supplementation inthe critically ill. Aprospective, randomized trial. Arch Surg 125:739-742, 1990

185. Wojtysiak SL, Brown RO, Robertson D, et al: Effect of hypoalbu-mmemia and parenteral nutrition on free water excretion and elec-trolyte-free water resorption. Crit Care Med 20:164-169, 1992

186. Rubin H, DeMeo M, Carlson 5, et al: Randomized, double-blind studyof intravenous human albumin in hypoalbuminemic patients receiv-ing TPN. JPEN 18:215, 1994

187. Rapp RP, Young B, Twyman D, et al: The favorable effect of earlyparenteral feeding on survival in head-injured patients. J Neurosurg58:906-912, 1983

188. Young B, Ott L, Thryman D, et al: The effect ofnutritional support onoutcome from severe head injury. J Neurosurg 67:668-676, 1987

189. Hausman D, Mosebach KO, Caspari R, et al: Combined enteral-

parenteral nutrition versus total parenteral nutrition in brain-injuredpatients. A comparative study. Intensive Care Med 1 1:80-84, 1985

190. Borzotta AP, Pennings J, Papasadero B, et al: Enteral versusparenteral nutrition aftersevere closed head injury. J Trauma 37:459-

468, 1994

191. Hadley MN, Grahm TW, Harrington 1’, et al: Nutritional support and

neurotrauma A critical review of early nutrition in forty-five acutehead injury patients. Neurosurgery 19:367-373, 1986

192. Grahm TW, Zadrozny DB, Harrington T: The benefits of early jejunal

hyperalimentation in the head-injured patient. Neurosurgery 25:729-735, 1989

193. Cerra FB, Lehman 5, Konstantinides N, et al: Improvement in im-mune function in ICU patients by enteral nutrition supplementedwith arginine, RNA, and menhaden oil is independent of nitrogen

balance. Nutrition 7:193-199, 1991194. Bower RH, Cerra FB, Bershadsky B, et al: Early enteral administra-

tion ofa formula (Impact) supplemented with arginine, nucleotides,and fish oil in intensive care unit patients: Results of a multicenter,prospective, randomized, clinical trial. Crit Care Med 23:436-449,1995

195. Moore FA, Moore EE, Kudsk KA, et al: Clinical benefits of an im-muse-enhancing diet for early postinjury enteral feeding. J Trauma

37:607-615, 1994

196. Kudsk KA, Minard G, Croce MA, et al: A randomized trial ofisonitrogenous enteral diets after severe trauma Ann Surg 224:531-

543, 1996197. Brown RO, Hunt H, Mowatt-Larssen CA, et al: Comparison of spe-

cialized and standard enteral formulas in trauma patients. Pharma-

cotherapy 14:314-320, 1994198. Kemen M, Senkal M, Mumme A, et al: Early postoperative

immunonutrition: clinical outcome and cost-benefit analysis [Ab-stractl. JPEN 20:245, 1996

199. Cerra FB, Shronts EP, Konstantinides NN, et al: Enteral feeding insepsis: Aprospective, randomized, double-blind trial. Surgery 98:632-

639, 1985

200. Garcia-DeLorenzo A, Planas M, Ortiz Lebya C, et al: Effects of dif-

ferent amounts of branched-chain amino acids in septic patients: Amulticenter trial. JPEN 18:215, 1994

201. von Meyenfeldt MF, Soeters PB, Vente JP, et al: Effect of branchedchain amino acid enrichment of total parenteral nutrition on nitro-gen sparing and clinical outcome of sepsis and trauma: A prospec-tive randomized double blind trial. Br J Surg 77:924-929, 1990

202. Jim#{233}nezJim#{233}nezFJ, Ortiz Leyba C, Morales M#{233}ndez5, et al: Pro-spective study on the efficacy ofbranched-chain amino acids in sep-

tic patients. JPEN 15:252-261, 1991203. Bower RH, Vallgren 5, LaFrance R, et al: Branched chain amino acid-

enriched solutions in the septic patient. A randomized, prospectivetrial. Ann Surg 203:13-20, 1986

204. Cerra FB, McPherson JP, Konstantinides FN, et al: Enteral nutritiondoes not prevent multiple organ failure syndrome (MOFS) after sep-sis. Surgery 104:727-733, 1988

205. Herndon DN, Stein MD, Rutsn TC, et at: Failure ofTPN supplemen-

tation to improve liver function, immunity, and mortality in ther-mally injured patients. J Trauma 27:195-204, 1987

206. Herndon DN, Barrow RE, Stein M, et al: Increased mortality withintravenous supplemental feeding in severely burned patients. J BurnCare Rehab 10:309-313, 1989

207. Liljedahl SO, Larsson J, Schildt B, et al: Metabolic studies in severeburns. Clinical features, routine biochemical analyses, nitrogen bal-ance and metabolic rate. Acts Chir Scand 148:393-400, 1982

208. Brown RO, Buopane EA, Vehe KL, et al: Comparison of modifiedamino acids and standard amino acids in parenteral nutrition sup-port ofthermally injured patients. Crit Care Med 18:1096-1 101, 1990

209. Chiarelli A, Enzi G, Casadei A, et al: Very early nutrition supplemen-

tation in burned patients. Am J Chin Nutr 51:1035-1039, 1990210. AlexanderJW, MacMillan BG, Stinnett JD, et al: Beneficial effects of

aggressive protein feeding in severely burned children. Ann Surg192:505-517, 1980

211. Jenkins ME, Gottschlich MM, Warden GD: Enteral feeding during

operative procedures in thermal injuries. J Burn Care Rehab 15:199-205, 1994

212. Garrell DR, Razi M, Lariviere F, et al: Improved clinical status andlength of care with low-fat nutrition support in burn patients. JPEN19:482-491, 1995

213. Gottschlich MM, Jenkins M, Warden GD, et al: Differential effects ofthree enteral dietary regimens on selected outcome variables in burnpatients. JPEN 14:225-236, 1990

214. Al-Sandy NM, Blackmore CM, Bennett ED: High fat, low carbohy-drate, enteral feeding lowers PaCO2 and reduces the period of venti-lation in artificially ventilated patients. Intensive Care Med 15:290-

295, 1989215. van den Berg B, Bogaard JM, Hop WCJ: High fat, low carbohydrate,

enteral feeding in patients weaning from the ventilator. IntensiveCare Med 20:470-475, 1994

216. Battistella FD, Widergren JT, Anderson JT, et al: A prospective ran-

domized trial of intravenous fat emulsion administration in traumavictims requiting total parenteral nutrition. J Trauma 39:164, 1995

217. Gunn T, Reaman G, Outerbridge EW, et al: Peripheral tots1 parenteral

nutrition for premature infants with the respiratory distress syn-drome: A controlled study. J Pediatr 92:608-613, 1978

218. Abel RM, Beck CH Jr, Abott WM, et al: Improved survival and acuterenal failure after treatment with intravenous essential L-amino ac-ids and glucose. Results ofaprospective, double-blind study. N Engl

J Med 288:695, 1973219. Leonard CD, Luke RG, Siegel RR: Parenteral essential amino acids

in acute renal failure. Urology 6: 154-157, 1975

220. Feinstein El, Blumenkrantz MJ, Healy M, et al: Clinical and mets-bolic responses to parenteral nutrition in acute renal failure. A con-trolled double-blind study. Medicine 60: 124-137, 1981

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221. Feinstein El, Kopple JD, Silberman H, et al: Total parenteral nutri-tion with high or low nitrogen intakes in patients with acute renal

failure. Kidney mt 24:5319-5323, 1983222. Mirtallo JM, Schneider PJ, Mavko K, et al: A comparison of essential

and general amino acid infusions in the nutritional support of pa-tients with compromised renal function. JPEN 6:109-113, 1982

223. Mehts RL: Therapeutic alternatives to renal replacement for criti-cally ill patients in acute renal failure. Semin Nephrol 14:64-82, 1994

224. Wolfson M, Jones MR, Kopple JD: Amino acid losses during hemo-

dialysis with infusion ofamino acid and glucose. Kidney Int 21:500-506, 1982

225. IkizlerTA, Flakoll PJ, Parker HA, et al: Amino acid and albumin lossesduring hemodialysis. Kidney Int 46:830-837, 1994

226. Fan 5, Lau W, Wong K, et al: Ike-operative parenteral nutrition in

patients with oesophageal cancer: A prospective, randomised clini-cal trial. Clin Nutr 8:23-27, 1989

227. Thompson B, Julian T, Stremple J: Perioperative total parenteral nu-

trition in patients with gastrointestinal cancer. J Surg Res 30:497-450, 1981

228. MullerJ, Keller H, Brenner U, et al: Indications and effects of preop-erative parenteral nutrition. World J Surg 10:53-63, 1986

229. Bellantone R, Doglietto G, Bossola M, et al: Preoperative parenteralnutrition in the high risk surgical patients. JPEN 12: 195-197, 1988

230. Muller J, Brenner U, Dienst C, et al: Preoperative parenteral feedingin patients with gastrointestinal carcinoma Lancet 1:68-71, 1982

231. Smith R, Hartemink R: Improvement of nutritional measures during

preoperative parenteral nutrition in patients selected by the prog-nostic nutritional index: A randomized controlled trial. JPEN 12:587-

91, 1988232. Heatley RV, Williams RHF� Lewis MH: Pre-operative intravenous feed-

ing: A controlled trial. Postgrad Med J 55:541-545, 1979

233. Fan 5, Lo C, Lai E, et al: Perioperative nutritional support in pa-tients undergoing hepatectomy for hepatocellular carcinoma N Engl

J Med 331:1547-1552, 1994234. Meguid M, Curtas M, Meguid V, et al: Effects of pre-operative TPN

on surgical risk-preliminary status report. Br J Clin Prac

42(Suppl):53-58, 1988

235. Bellantone R, Doglietto G, Bossola M, et al: Preoperative parenteralnutrition of malnourished patients. Acta Chir Scand 1988;22:249-

251, 1988

236. Moghissi K, Hornshaw J, Teasdale P, et al: Parenteral nutrition incarcinoma of the oesophagus treated by surgery: Nitrogen balance

and clinical studies. Br J Surg 64:125-128, 1977

237. Abel R, Fischer J, Buckley M, et al: Malnutrition in cardiac surgicalpatients: Results of a prospective randomized evaluation of early

postoperative parenteral nutrition. Arch Surg 111:45-50, 1976

238. Preshaw R, Attisha R, Hollingworth W: Randomized sequential trialof parenteral nutrition in healing of colonic anastomoses in man.Can J Surg 22:437-439, 1979

239. Woolfson A, Smith J: Elective nutritional support after major sur-gery: A prospective randomized trial. Clin Nutr 8:15, 1989

240. Holter A, Fischer JE: The effects ofperioperative hyperalimentationon complications in patients with carcinoma and weight loss. J Surg

Res23:31-37, 1977

241. Jensen 5: Clinical effects of enteral and parenteral nutritionpreceeding cancer surgery. Med Oncol Tumor Pharmacother 2:225-

229, 1985

242. Collins J, Oxby C, Hill G: Intravenous amino acids and intravenoushyperalimentation as protein-sparing therapy after major surgery:A controlled clinical trial. Lancet 1:778-791, 1978

243. Reilly J, Mehta R, Teperman L, et al: Nutritional support after livertransplantation: A randomized prospective study. JPEN 14:386-391,

1990

244. von Meyenfeldt M, Meijerink W, Rouflart M, et al: Perioperative flu-tritional support: a randomised clinical trial. Clin Nuti 11:180-186,

1992

245. Shukla HS, Rao RR, Banu N, et al: Enteral hyperalinientation in mal-nourished surgical patients. Indian J Med Res 80:339-346, 1984

246. 1Am S, Choa R, Lam K, et al: Total parenteral nutrition versus gas-

trostomy in the preoperative preparation of patients with carcinomaof the esopagus. Br J Surg 68:69-72, 1981

247. Sagar S, 1-larland P, Shields R: Early postoperative feeding with el-ernental diet. Br Med J 1:293-295, 1979

248. Ryan JA, Page CP, Babcock L: Early postoperativejejunal feeding ofelemental diet in gastrointestinal surgery. Am Surgeon 47:393-403,

1981249. Smith RC, Hartemink RJ, Hollinshead JW, et al: Fine bore jejunos-

tomy feeding following major abdominal surgery: A controlled ran-

domized clinical trial. Br J Surg 72:458-461, 1985

250. Iovinelli G, Marsili I, Varrassi G: Nutrition support after total laryn-gectomy. JPEN 17:445-448, 1993

251. Daly JM, Lieberman MD, Goldfme J, et al: Enteral nutrition with

supplemental arginine, RNA, and omega-3 fatty acids in patients af-ter operation: Immunologic, metabolic and clinical outcome. Sur-

gery 112:56-67, 1992252. Koretz RL: Immunonutrition? Gastroenterology 104:936-938, 1993253. Bastow MD, Rawlings J, Allison 5: Benefits of supplementary tube

feeding after fractured neck of femur: A randomized controlled trial.BrMedJ 187:1589-1592, 1983

254. Delmi M, Rapin C-H, Bengoa J-M, et al: Dietary supplementation in

elderly patients with fractured neck of the femur. Lancet 335:1013-

1016, 1990

255. DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin

Thals7:177, 1986

256. Wolfe BM, Mathiesen KA Clinical practice guidelines in nutrition sup-port: Can they be based on randomized clinical trials?JPEN 21:1-6,1997

257. Pillar B, Perry S. Evaluating total parenteral nutrition: Final report

and core statement of the Technology Assessnient and PracticeGuidelines Forum, Program on Technology and Health Care, De-partment of Community and Family Medicine, Georgetown Univer-sity School of Medicine, Washington, DC, 1990

APPENDIX

Planning Committee: Bruce Bistrian, MD, PhD, Beth Is-rael Deaconess Medical Center, Harvard Medical Center,Boston, MA; Albert Bothe Jr, MD, University of ChicagoMedical Center, Chicago, IL; Margaret Heitkemper, RN,PhD, University of Washington, Seattle, WA; Van Hubbard,MD, PhD, National Institute of Diabetes, and Digestive andKidney Diseases, Bethesda, MD; David Schnackenberg,PhD, ASCN, Bethesda, MD.

Conference Coordinator: Edward Bernstein, MPH,A.S.P.E.N., Silver Spring, MD.

Invited Participants: John Kinney, MD, Rockefeller Uni-versity, New York, NY (Conference Chairman); SamuelKlein, MD, Washington University School of Medicine, St.Louis, MO (Conference Co-Chairman).

Nutrition Assessment Group: Khursheed Jeejeebhoy, MB,BS, PhD, St. Michael’s Hospital, Toronto, Ontario, Canada(group leader); Michael Hambidge, MD, ScD, Universityof Colorado Medical Center, Denver, CO; StevenHeymsfield, MD, St. Luke’s Roosevelt Hospital, New York,NY; Carol Ireton-Jones, PhD, RD, CORAM Healthcare,

Carrollton, TX; Marsha Wolfson, MD, Baxter HealthcareCorp, McGaw Park, IL.

Perioperative Patients Group: Patrick Twomey, MD, SanFrancisco Veterans Administration Medical Center, SanFrancisco, CA (group leader); Danny Jacobs, MD, Brighamand Women’s Hospital, Boston, MA; Joyce Keithley, DNSc,RN, Rush Medical Center, Chicago, IL; Michael Meguid,

MD, SUNY Health Sciences Center, Syracuse, NY; SusanPingleton, MD, tJniversity of Kansas Medical Center, Kan-sas City, KS.

Critical Illness Group: Michael Murray, MD, Phi), MayoClinic, Rochester, MN (group leader); Joel Kopple, MD,

Harbor-UCLA Medical Center, Torrance, CA; RonaldKoretz, MD, olive View Medical Center, Sylmar, CA; Rob-ert Shulnian, MD, Baylor College of Medicine, Houston,

TX; Douglas Wilmore, MD, Brigham and Women’s Hospi-tal, Boston, MA.

Gastrointestinal Disease Group: David Alpers, MD,Washington University School of Medicine, St. Louis,

MO (group leader); David Driscoll, PhD, RPh, Beth

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Israel Deaconess Medical Center, Boston, MA; C. Rich-ard Fleming, MD, Mayo Clinic, Jacksonville, FL; Harry

Greene, MD, Slim-Fast Food Co, West Palm Beach, FL;Michael Sitrin, MD, University of Chicago, Chicago, IL.

Wasting Disease Group: Marc Hellerstein, MD, PhD, Uni-versity of California, Berkeley, Berkeley, CA (groupleader); Virginia Herrmann, MD, St. Louis University

School of Medicine, St. Louis, MO; Timothy Lipman, MD,Department of Veterans Affairs Medical Center, Wash-ington, DC; Donald Mock, MD, PhD, University of Arkan-

sas for Medical Sciences, Little Rock, AR.Other Contributors: Peggy Borum, PhD, University of

Florida, Gainesville, FL; Eva Shronts, MMSc, RD, Uni-versity of Minnesota, Minneapolis, MN.

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Documents

Nutrition Support in Clinical Practice: Review of Published Data and