Evidence Base for Specialized Nutrition Support

Nutrition Grand Rounds September 2000: 282-289

Evidence Base for Specialized Nutrition Support ChristopherAshley, M.D., andLynHoward,M.B., F.R.C.P.

Data regarding the use of both parenteral and enteral specialized nutritional support (SNS) are available for a variety of common clinical scenarios. Herein, the data are reviewed for SNS in the con- text of critical illness, perioperative care, wasting syndromes (including HIV disease and cancer), and gastrointestinal disease (including short bowel syndrome, inflammatory bowel disease, and pancreatitis).

4

Introduction

In the later part of the 20th century, specialized nutrition support (SNS), both parenteral nutrition (PN), delivered through an intravenous catheter, and enteral nutrition (EN), delivered through a tube in the intestine, matured from “show-and-tell” to a more systematic science. Things have progressed enough so that it is now possible to summa- rize where these therapies appear to be beneficial, where they are not, and where the jury is still out. This information is presented here around a series of clinical vignettes that are common in medical-surgical practice.

There are two areas where information is sparse about the use of SNS. First, we do not know the length of time SNS can safely be withheld. For ethical reasons, SNS is rarely compared with no nutrition support. Usually control patients receive standard care, which is whatever they can tolerate by mouth, with or without intravenous hypocaloric glucose.

The second gap relates to the true effectiveness and cost of tube enteral nutrition.’ Many studies have shown that EN has fewer complications than PN, but this may relate to avoidable PN complications caused by parenteral ovemutrition. EN may be safer than PN, but it may not be safer than no SNS, and scientifically designed formulas may not be better than blenderized whole food given by tube. Such controls are not part of most study protocols. The cost of EN also may be higher than generally thought. Modem EN frequently requires endoscopic, radiologic,

Drs. Ashley and Howard are with the Department of Medicine, Division of Clinical Nutrition and Pediatric Gastroenterology, Albany Medical College, Albany, NY 12208-3479, USA.

or surgical placement of the feeding tube. The real cost of obtaining and sustaining such access has been only oc- casionally documented.’

Although providing oral fluids and food is part of basic medical care, SNS, because it is associated with risk and discomfort, should only be recommended if treating malnutrition will favor a better outcome, and only with the patient’s consent. Starting SNS to avoid or redress malnutrition is active t reah~ent ,~ .~ similar to starting dialysis for renal failure. Diagnosing clinically significant malnutrition is a topic unto itself and is well reviewed el~ewhere.~,~ ’ Case-based Review of Evidence

This review will not cover every clinical situation. It will deal with four main patient categories: critical illness, perioperative ;are, wasting syndromes, and gastrointestinal disorders.

Critical Illness and SNS The patient was a 65-year-old man with a past medical history of chronic obstructive pulmonary disease and an 80 pacWyear history of smoking, admitted with lobar pneumonia. Within 24 hours of admission his respiratory status declined to the point that he required mechanical ventilation. He was in the ICU for an additional 36 hours and was known to have pneumococcal pneumonia and sepsis. According to his family his health had been declining for several months, as evidenced by insidious weight loss of at least 20 Ibs.

The questions are: Should SNS be started in this patient, and if so, by what route?

Although the effective timing of nutritional intervention is not known, because this patient was malnourished from the outset, tradition would dictate starting support sooner rather than later.

A recent meta-analysis of 26 prospective randomized controlled trials (PRCT) involving 22 1 1 patients with critical illness showed no clear benefit of PN over standard care. There was a trend toward reduction of complications in malnourished patients with PN. Complications were higher in patients whose treatment included parenteral lipids.’

Ameta-analysis of 1 1 PRCTs (966 patients) compared EN using formulas supplemented with key nutrients (Table

282 Nutrition Reviews@, Vol. 58, NO. 9

1) with EN using standard formulas. The analysis showed that EN with the supplemented formulas resulted in a significant reduction in infectious complications and length of hospital stay. The supplemented formula had no effect on mortality.8

In the critically ill, 65-year-old patient described here, EN with a formula providing key or conditionally essential nutrients would appear to be the best treatment option.

Patients who require mechanical ventilation usually require frequent airway suctioning, which can provoke gastric regurgitation. The tracheal cuff of an endotracheal or tracheostomy tube does not totally protect the patient against aspiration. EN feeding into the stomach or proximal duodenum has been shown to increase the risk of a~piration,~ a complication that can be lethal. As a conse- quence, the challenge is to insert the feeding tube in the distal duodenum or proximal jejunum. There are several methods for doing this. ZalogaIo described a blind bedside technique, confirming small bowel placement by bile aspiration. Using this technique, approximately 60% of tubes reached the distal duodenum or proximal jejwum. The average time for placement was 40 minutes. Patrick et al." described a bedside endoscopic technique. In 94% of patients, the tube reached the distal duodenum or jejunum. The average procedure time was 12 minutes. In chronic conditions, more permanent jejunal access may be appro- priate using percutaneous radiologic, endoscopic, or sur-

gical techniques.'* All of these tubes can provide jejunal access for feeding and simultaneous gastric access for decompression. Achieving and sustaining jejunal enteral access is expensive and underscores the point made pre- viously about the potentially high cost of modern enteral feeding.

Perioperative SNS The patient was a 78-year-old man with diabetes and dif- fuse peripheral vascular disease who presents with decubitus ulcers, wasting, and a painful, dusky, pulseless left lower extremity with dry gangrene of the toes and a line of margination at the forefoot.

The question is: Should SNS be started preoperatively or postoperatively?

In many surgical patients, operative intervention cannot be delayed. In some, the surgical timing is more elective, and the issue of preoperative build-up of a cachectic patient is important. It has been known since Studley's classic paper13 in 1936 that there is a strong correlation between preoperative malnutrition and postoperative complications and mortality. It is not clear whether the close association is a flag signaling a sicker patient or if the association points to cause and effect. Many studies have been undertaken, especially with parenteral nutrition, to determine if improving a patient's preoperative nutritional status favors better operative outcome. A recent pooled

Table 1. Conditionally Essential Nutrients Nutrient Metabolic Function Glutamine

Nucleotides

Arginine

Branched-chain amino acids

Sulfur-containing amino acids Methionine

-1

-1 S-adenosyl methionine (SAM)

Homoc steine r Cysteine -+ glutathione

taurine carnitine

Fuel for enterocytes and immunocytes; preserves hepatic glutathione.

Derivatives (cyclicAMP, cyclicGMP) serve as mediators for many metabolic processes.

Enhances lymphocyte cytotoxicity via nitric oxide; substrate for polyamine synthesis; promotes protein synthesis via release of human growth hormone.

Level in muscle regulates muscle-protein breakdown; decreased in catabolic patients, especially those with liver disease.

Glutathione is chief cytoplasmic free radical scavenger; taurine conjugates bile salts; carnitine transports fatty acids into mitochondria for R-oxidation; S A M donates methyl group to choline and creatine; choline normalizes cell wall fluidity.

Short-chain fatty acids

Omega-3 fatty acids

Derived by bacterial breakdown from soluble fibers such as pectin; fuel for enterocytes, particularly colonocytes.

Promote production of prostaglandins and leukotrienes of N-3 series (PGE,, LTB,, etc.) and reduce production of prostaglandins and leukotrienes from N-6 series (PGE,, LTB,, etc.), which are proinflammatory.

Source: from Howard L. Parenteral and enteral nutrition therapy. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, eds. Harrison's principles of internal medicine, 14th ed. New York, 1998;472-80. Used with permission of the publisher, The McGraw- Hill Companies.

Nutrition Reviews@, Vol. 58, No. 9 283

analysis of 13 PRCTs evaluated 1250 moderately or severely malnourished patients given PN or standard care for 7-1 0 days preoperatively. Although the pooled results showed no difference in operative mortality, it did show in patients given PN a 10% reduction in postoperative complications, lowering them from 40% to 30%.6

Five PRCTs compared preoperative build-up by enteral nutrition with an ad libitum oral diet. In three studies the supplement was give by tube,l”16 and in two it was taken by mouth.”J8 The 460 patients studied all had cancer. Preoperative EN patients had a 2540% reduction in major postoperative complications. The length of hospital stay was also reduced in the two studies in which it was r e p ~ r t e d . ~ ~ , ’ ~ On the down side, half of the EN patients had some symptoms of gastrointestinal intolerance, and 20% had enteral catheter dysfunction.

Most patients who warrant preoperative SNS are as- sumed to warrant postoperative SNS. In fact, in the PRCTs included in the preoperative PN pooled analysis cited,6 all patients continued the PN postoperatively. But what hap- pens if surgical intervention is urgent and SN9 can only be started postoperatively? In a meta-analysis of 8 PRCTs involving 725 surgical patients, routine postoperative PN in patients who had some marker of nutritional impairment (weight loss > lo%, serum albumin < 3.5 g/dL) resulted in a 10% increase in complications.6

The largest study was done in Sweden and involved 300 patients who hadmajor surgery or abdominal trauma.19 On the first postoperative day they were randomized to PN or hypocaloric glucose. Sixty percent ofthese patients resumed oral eating by 8-9 days, and their outcome was not better or worse on PN. In the 40% of patients with more prolonged inability to eat, the outcome was compli- cated. Those on glucose alone for 14 days or longer had increased mortality and increased severe complications. This type of information is rarely available but is important because it tells us that in postoperative patients, semistarvation beyond 10-12 days is clearly unwise. In the PN group, approximately half the patients requiring prolonged support were benefited and half had a higher risk of complications. The risk derived chiefly from metabolic complications related to overnutrition. This result emphasizes the importance of strict PN metabolic monitoring. Unfortunately, the Swedish investigators could not pinpoint in advance which patients were at risk for delayed recovery of gut function. Although this study makes it clear that routine initiation of PN in the average postoperative patient is unwise, knowing when to provide PN is still a difficult clinical judgment.

Postoperative EN has been studied from three sepa- rate angles. First, routine early jejunal tube feeding has been compared with simple advancement of the oral diet. The aggregate data from four PRCTs (142 patients, most with cancer) showed no benefit from this jejunal feeding in terms of reducing postoperative morbidity and mortal-

ity.6 Second, early EN has been compared with early PN,2O and here the aggregate data from eight PRCTs (230 patients, most with abdominal trauma) showed EN was associated with significantly fewer septic complications than PN (1 8% versus 35%). Third, EN using formulas with key nutrients (Table 1) has been compared with standard enteral formulas in six PRCTS.~’-~~ Patients receiving the supplemented EN formulas had significantly fewer postoperative infectious complications. (These six studies were included in Heys et al.’s meta-analysis of critical illness.8)

These results suggest that the depleted diabetic patient with dry gangrene and decubitus ulcers would benefit from perioperative SNS, especially if provided by the enteral route. He might benefit from a formula with key nutrients, but if glucose intolerance was a major problem, there are diabetic EN formulas modified to include more monounsaturated fatty acids and less carbohydrate calories. These formulas have been shown to reduce the diabetic patient’s glucose and lipid abnormalities in short- term s t ~ d i e s . ~ ~ , ~ ~ In addition, zinc and vitamin C sugple- ments are known to improve healing of decubitus u l c e r ~ , 2 ~ ~ ~ and vitamin C reduces protein glyc~sylation.~~ All of these factors could be helpful to our diabetic patient.

Wasting Syndromes and SNS Wasting of-lean body mass occurs either because there is insufficient intake and assimilation of nutrients or as a result of hypermetabolism. Insufficient intake can occur because of anorexia, inability to swallow, or inability to absorb ingested nutrients. Hypermetabolism can occur because of cytokines or altered regulatory hormones.

Wasting is characteristic of many illnesses, but it is a major feature of human immunodeficiency virus (HIV) disease and cancer. Clinically, severe wasting always evokes the question: Does SNS intervention help?

HIVdisease and SNS. The patient was a 34-year-old HIV positive woman who is CDC class C3, and her most recent viral load was 150,000. She has been compliant with her medical regimen and has been closely followed for 10 years. Until a few months prior to admission, her viral load was well controlled. Since that time her viral load steadily increased despite adjustments in therapy. She presented to her physician complaining of weight loss, anorexia, and fatigue. She is cachectic at 5 ft 6 ins and 85 lbs.

Two PRCTs have looked at the role of SNS in HIV wasting. Melchior et al.32 randomized 3 1 malnourished and severely immunodepressed HIV patients to home PN or dietary counseling. Six patients died during the study, three in each group. Despite a lack of effect on mortality, the SNS group had significant improvement in lean body mass, which was associated with a better quality of life. Subsequently, survival was tracked in 26 patients who stayed in their original randomized group. Median survival with home PN was 199 days and with dietary counseling 57 days?3 This potentially important SNS benefit

284 Nutrition Reviews@, Vol. 58, No. 9

awaits confirmation from other centers. Kotler and his colleagues reported somewhat differ-

ent findings.34 In a series of studies they showed that SNS can restore lean body mass in HIV patients who have a barrier to eating (e.g., severe oral or esophageal candidi- asis) or to absorption (e.g., intestinal cryptosporidiosis or microsporidiosis). SNS cannot restore lean body mass when the wasting is due to systemic infection. In a PRCT of HIV patients with malabsorption, home PN was not more effective than an isocaloric semielemental oral supplement, and survival in both groups was ~imilar.3~ The patients randomized to the oral supplement experienced a better quality of life and their therapy costs were much less.

These apparently conflicting results suggest a need for more HIV SNS PRCTs, perhaps with more stringent criteria for the type of wasting involved and with compari- sons of home PN not only with dietary counseling or oral supplements but also with home EN with key nutrients.

There have been a number of trials in HIV pgients evaluating appetite s t imu lan t~ ,3~~~~ anabolic steroid^,^',^^ and growth These substances improved body weight and a sense of well-being but did not change survival.

After the 34-year-old HIV patient has been evaluated for gastrointestinal or systemic infection, SNS may be ap- propriate. The data suggest it would be reasonable to start with oral supplements and appetite stimulants and progress to EN or PN if the patient so chooses.

Cancer andSNS. The patient was a 52-year-old home- less woman who presented with upper abdominal pain and jaundice and was diagnosed with cancer at the head of the pancreas. She underwent a Whipple procedure and was scheduled to receive a course of radiotherapy, but it was put on hold because her weight fell from 1 15 lbs. to 92 lbs., and she was eating less than 500 calories a day.

The question is: Should SNS be part of her management?

Early nonrandomized studies suggested a role for SNS in patients with cancer cachexia. Subsequent randomized studies have not confirmed this benefit and in fact have shown a higher rate of sepsis in cancer patients treated with PN compared with ~ont ro ls .4~ ,~ These findings led to the publication of a position statement by the American College of Physicians in 1989 advising against routine use of PN in cancer patients undergoing

More recently, Klein and Koree6 reviewed more than 70 PRCTs (> 4000 patients) evaluating SNS in cancer patients. They note potential problems with many of these studies, such as inclusion of different tumor types and stages of disease, exclusion of severely malnourished patients, inclusion of patients with normal nutrition, and use of only survival and complications as endpoints with no assessment of quality of life. Despite these limitations, it is clear that these studies confirm an overall lack of

benefit of SNS in cancer treatment. However, there are a few exceptions.

First, malnourished cancer patients undergoing surgery benefit, similar to noncancer surgical patients, from preoperative build up (see the section “Perioperative SNS”). Second, hematologic and gastrointestinal side effects of radiation for abdominal and pelvic cancer lessen in patients receiving EN.47,48 Third, patients undergoing bone marrow transplantation (BMT) appear to benefit from SNS. A PRCT (137 patients) done by Weisdorf et al.49 at the University of Minnesota showed that although PN in the cytoreductive phase did not alter acute in-hospital complications, it did increase overall survival and time to relapse. Median survivals were 2 1 and 7 months, respectively, for the PN versus control group patients.49 This remarkable finding deserves further investigation. Another PRCT (61 patients) carried out by Szeluga et al.” compared EN with PN in BMT patients. Seventy-seven percent of the patients randomized to EN were able to com- plete a 28-day course of treatment; however, 73% of these patients needed additional intravenous fluid support. ECJ was associated with fewer complications and lower cost. Survival and bone marrow recovery did not differ between patient groups supported by these two forms of SNS.

Because glutamine is an important gut fuel, it has been hypothesized that adding it to PN might reduce gut bacterial translocation and sepsis in BMT patients. Two PRCTs evaluated this concept. The study by Zeigler et al.sl showed that glutamine added to PN reduced the infection rate and shortened hospital stay but did not alter 3-month survival. Schloerb and Amare’s studys2 confirmed this result, but only when major outliers were excluded.

A PRCT by Charuhas et al.53 compared home PN with simple home intravenous hydration in BMT patients. This study found that home PN resulted in less weight loss, but it delayed resumption of oral feeding, whereas the patients on simple hydration, although they lost more weight, suffered no adverse consequences.

In the patient with pancreatic cancer awaiting radiotherapy, once diabetes is ruled out and pancreatic enzymes and appetite stimulants are tried, continuing weight loss would appear to justify some form of EN because this provides nutrition support and lessens the hematologic and gastrointestinal side effects of the planned radiation treatment.

Gastrointestinal Disease and S NS Disease of the gastrointestinal tract (GIT) presents double jeopardy, because on the one hand GIT disease directly affects nutritional status by limiting food intake and absorption, and on the other hand normal gut repair and growth depends on luminal nutrients. The gut mucosa is a large interface between the internal milieu and external toxic substances and microbes. The gut mucosal cells turn over every 3 to 4 days.

Nutrition Reviews@, Vol. 58, No. 9 285

Short bowel syndrome and SNS. The patient was a 5 1 -year-old man who suffered an idiopathic mesenteric vein thrombosis 10 years earlier that required resection of the bowel 20 cm beyond the ligament of Treitz to the midtransverse colon. He infused PN at home and at last report needed it four nights per week. He ate a low-lac- tose, low-fat diet and had four to seven loose stools per day.

The question is: Could he be weaned off this expensive therapy?

Before the advent of PN, patients with acute short bowel syndrome resulting from extensive surgical resection seldom survived. PN has allowed patients with only 10% of small bowel remaining to survive indefinitel~.~~ SNS PRCTs are believed to be unethical in the acute situation, but stable long-term patients have been studied in a few randomized protocols. A small PRCT has shown choline supplementation reduces hepatic dysfunction in home PN patients.55 Using patients as their own controls, a pre- liminary study suggested parenteral human growth hormone and oral glutamine improved bowel adaptatizn and enabled long-term PN patients to graduate from PN to an oral diet.56 This concept was tested by Scolapio et al.57 in a formal PRCT, but no major improvement occurred with growth hormone or oral glutamine in patients with long- standing short bowel syndrome consuming a relatively normal oral diet.

Our long-term home PN patient presented here has already graduated from total to partial dependence on parenteral support. The data do not suggest further adap- tation could be obtained by short-term use of parenteral growth hormone and pharmacologic doses of oral glutamine. It is possible he could be kept compensated by the use of overnight EN feeds, allowing around-the-clock use of his limited GIT.

Inflammatory bowel disease and SNS. The patient was a 16-year-old boy with Crohn’s disease and symptoms of subacute small bowel obstruction who acutely lost 12 Ibs. in a month and had a serum albumin of 2.9 gl dL. He was on the 10th percentile for height despite two moderately tall parents. His most recent admission was for a trial of parenteral steroids and possible surgery if his obstructive symptoms did not improve.

The questions are: Does he require bowel rest and parenteral nutrition, or could an enteral drip be tried, and if so, does the type of enteral formula matter?

Three meta-analyses of published PRCTs5- have concluded that corticosteroids are more effective than EN in inducing and sustaining remissions in patients with acute Crohn’s disease (80% versus 60% achieving remission). In addition, the pooled data showed that elemental diets using simple amino acids are not superior to poly- meric diets using peptides or a single whole protein. Al- though these results weigh against the concept that Crohn’s inflammation is exacerbated by sensitivity to cer-

tain food proteins, Riordan et a1.6i have shown in a PRCT that there still may be some truth in this concept. They found that Crohn’s patients on a diet excluding foods that cause gastrointestinal upset have longer remissions than those on corticosteroids who return to unlimited eating.

Three PRCTs have shown that bowel rest is not necessary to achieve a clinical remission. Patients maintained on their baseline Crohn’s medication did equally well with bowel rest and PN, EN, or oral diet.62*

Three PRCTs have examined SNS as adjunctive treatment to steroids in Crohn’s colitis and ulcerative colitis. These studies showed that PN and bowel rest were not better than EN or regular diet at inducing remission or avoiding

In the 16-year-old boy with Crohn’s disease, an enteral drip would seem worth a try, and if this is not toler- ated then PN is indicated because of his substantial weight loss and possible need for surgery. Because he also had parameters of chronic growth failure, if he responds to treatment but still has a limited oral intake, overnight supplemental tube feeds may be advisable to promo& catch-up growth before his epiphyses fuse.68

Acute pancreatitis and SNS. The patient was a 56- year-old man with known pancreatic insufficiency and mild diabetes following many years of chronic excessive alco- hol intake. He was admitted with acute onset of abdominal pain and vomiting following a drinking bout. He had epi- gastric tenderness but no mass. His serum amylase and lipase were 830 IU/L and 460 IUL, respectively. His serum albumin was 2 g/dL.

The questions are: Should this patient receive SNS, and if he receives PN, can intravenous fat emulsion be part of his formula?

Traditional thinking is that any enteral intake stimu- lates the pancreas and exacerbates the inflammatory pro- cess. For this reason PN and nasogastric suction are com- monly instituted.

Recent s t u d i e ~ ~ ~ , ~ ~ have shown that mild or moderate pancreatitis, as assessed by Ranson’s criteria or computed tomographic scanning, accounts for 80-90% of patients with this disease. A PRCT found no benefit from PN for patients with this mild to moderate disease, and PN was associated with increased likelihood of sepsis and increased length of hospital stay.7i

Severe pancreatitis, by contrast, is associated with high mortality, especially if there is significant depletion of lean body Under these circumstances some form of SNS may be life saving. Two PRCTs compared PN with EN.73,74 The EN used a semielemental diet infused into the proximal jejunum. Both PN and jejunal EN have been documented to cause minimal pancreatic stimulation. The two PRCTs involved only small numbers of patients, but both showed no difference in patient mortality. Septic complications were significantly lower with jejunal EN.

In severe pancreatitis, if serum triglycerides are not

286 Nutrition Reviews”, Vol. 58, No. 9

elevated, parenteral exogenous lipids appear to be safe.75 The patient had severe pancreatitis and substantial

wasting and likely requires prolonged SNS. Gastric suction is necessary, and EN feeding into the proximal jejunum would seem his best option, with parenteral fluids and electrolytes to support his diarrheal losses. If jejunal tube placement is not available, then PN should be instituted. If his diabetes is out of control, he may need an insulin drip. If his serum triglycerides are not significantly elevated, parenteral lipids may provide some of his calories.

Conclusion

This review of evidence-based medicine suggests that SNS needs to move away from PN and toward more EN, a potentially safer and more physiologic approach. Having made this general point, however, there are some necessary caveats. First, safe enteral nutrition frequently requires access to the distal duodenum or proximal jejunum, and this is not a widely available technique. As a conse- quence, PN may be the only SNS approach that is'practi- cal in many institutions. Second, SNS in patients requiring long-term support or repletion for elective surgery is best accomplished outside the hospital. Although reimbursement for home PN is usually fair, reimbursement for home EN is often woefully inadequate. This creates a major disincentive to the more rational approach.

Finally, the data suggest that many of the PN complications stem from overnutrition, perhaps too much zeal and not enough caution. It seems likely that these meta- analyses, showing greater complications with PN compared with EN, will stimulate tighter monitoring of and more modest calorie goals for PN-supported patients.

1.

2.

3.

4.

5.

6.

7.

8.

Lipman TO. Grains or veins: is enteral nutrition really better than parenteral nutrition? A look at the evidence. JPEN 1998;22:167-82 Ott L, Annis K, Hatton J, et al. Postpyloric enteral feeding costs for patients with severe head injury: blind placement, endoscopy, and PEG/J versus TPN. J Neurotrauma 1999;16(3):233-42 Dresser RS, Boisaubin EV. Ethics law and nutritional support. Arch Intern Med 19853 45:122-4 Howard L. Parenteral and enteral nutrition therapy. In: Fauci AS, Braunwald E, lsselbacher KJ, Wilson JD, eds. Harrison's principles of internal medicine, 14th ed. New York: McGraw-Hill, 1998;472-80 Hill GL. Body composition research: implications for the practice of clinical nutrition. JPEN 19923 6:

Klein S, Kinney J, Jeejeebhoy K, et al. Nutrition support in clinical practice: review of published data and recommendations for future research di- rections. JPEN 1997;21:133-56 Heyland DK, MacDonald S, Keefe L, et al. Total parenteral nutrition in the critically ill patient: a meta- analysis. JAMA 1998;280:2013-9 Heys SD, Walker LG, Smith I, et al. Enteral nutri-

197-21 8

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

tional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg

Jacobs S, Chang RWS, Lee B, et al. Continuous enteral feeding: a major cause of pneumonia among ventilated intensive care unit patients. JPEN

Zaloga GI? Bedside method for placing small bowel feeding tubes in critically ill patients. Chest 1991 ;

Patrick PG, Marulendra S, Kirby DF, et al. Endo- scopic nasogastric-jejunal feeding tube placement in critically ill patients. Gastrointest Endosc

Barkmeier JM, Trerotola SO, Weibke EA, et al. Per- cutaneous radiologic, surgical endoscopic and percutaneous endoscopic gastrostomy/gastroje- junostomy: comparative study and cost analysis. Cardiovasc Intervent Radio1 1998;21:324-8 Studley HO. Percentage weight loss. A basic indi- cator of surgical risk in patients with chronic peptic ulcer. JAMA 1936;106:458-60 Shukla HS, Rao RR, Banu N, et al. Enteral hyperalimentation in malnourished surgical patients. \n- dian J Med Res 1984;80:339-46 Foschi D, Cavagnor G, Callioni F, et al. Hyperali- mentation of jaundiced patients on transhepatic percutaneous biliary drainage. Br J Surg 1987;154:

Von Meyenfeldt M, Meijerink W, Rouflart M, et al. Efficacy' of perioperative nutritional support. Lan- cet 1 992;340: 1 87-8 Flynn MB, Leightty FF. Preoperative outpatient nutritional support of patients with squamous cancer of the upper aerodigestive tract. Am J Surg

Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg 1999;134: 1309-1 6 Sandstrom R, Drott C, Hyltander A, et al. The effect of postoperative intravenous feeding (TPN) on outcome following major surgery evaluated in a randomized study. Ann Surg 1993;217:185-95 Moore FA, Feliciano DV, Andrassy RJ, et al. Early enteral feeding, compared with parenteral, reduces postoperative septic complications: the results of a meta-analysis. Ann Surg 1992;21(2):172-83 Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA and omega-3 fatty acids after operation: immunologic, metabolic and clinical outcome. Surgery 1992;112:

Braga M, Vignali A, Gianotti L, et al. Benefits of early postoperative enteral feeding in cancer patients. lnfusionstherapie und Transfusions Medizin

Daly JM, Weintraub F, Shou J, et al. Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg 1995;221:

Schilling J, Vranjes N, Fierz W, et al. Clinical outcome and immunology of postoperative arginine,

1999;229:467-77

1990;14:353-6

1 00: 1 643-6

1997;45:72-6

359-62

1987;154:359-62

56-67

1995;22:280-4

327-38

Nutrition Reviews", Vol. 58, No. 9 287

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low-calorie/low-fat IV solutions. Nutrition 1996;l 2:423-9 Braga M, Gianotti L, Vignali A, et al. Artificial nutrition after major abdominal surgery: impact of route of administration and composition of the diet. Crit Care Med 1998;26:24-30 Senkal M, MummeA, Eikhoff U, et al. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Crit Care Med 1997;25:1489-96 Grundy SM. Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cho- lesterol. New Engl J Med 1986;314:745-8 Garg A, Bantle JF: Henry RR, et al. Effects of vary- ing carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus. JAMA

Lewis B. Zinc and vitamin C in the aetiology of pressure sores. J Wound Care 1996;5:483-4 Taylor TV, Rimmer S, Day B, et al. Ascorbic acid supplementation in the treatment of pressure-sores. Lancet 1974;72(7880):544-6 Davie SJ, Gould BJ, Yudkin JS. Effegt of vitamin C on glycosylation of proteins. Diabetes 1992;41:

Melchior JC, Chastang C, Gelas P, et al. Efficacy of 2-month total parenteral nutrition in AIDS patients: a controlled randomized prospective trial. AIDS

Melchior JC, Gelas P, Carbonnel F, et al. Improved survival by home total parenteral nutrition in AIDS patients: follow up of a controlled randomized prospective trial. AIDS 1998;l 2:336-7 Kotler DF: Fogelman L, Tierney A. Comparison of total parenteral nutrition and an oral, semi-elemental diet on body composition, physical function, and nutrition-related costs in patients with malabsorption due to acquired immunodeficiency syndrome.

Von Roenn JH, Armstrong D, Kotler DP, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med 1994;121:393-9 Oster MH, Enders SR, Samuels SJ, et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med 1996;121:400-8 Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome. Ann Intern Med 1998;l 293 8-26 Miller K, Corcoran C, Armstrong C, et al. Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab 1998;83:

Lee PDK, Pivarnik JM, Bukar JG, et al. A randomized, placebo-controlled trial of combined insulin- like growth factor I and low-dose growth hormone therapy for wasting associated with human immunodeficiency virus infection. J Clin Endocrinol Metab 1996;81:2968-75 Waters D, Danska J, Hardy K, et al. Recombinant human growth hormone, insulin-like growth factor I, and combination therapy in AIDS-associated wasting. Ann Intern Med 1996;l 253365-72

1994;271 : I4214

167-73

1996;l 0:379-84

JPEN 1998;22:120-6

271 7-25

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

Schambelan M, Mulligan K, Grunfeld C, et al. Re- combinant human growth hormone in patients with HIV-associated wasting: a randomized, placebo- controlled trial. Ann Intern Med 1996;125:873-82 Clark RH, Feleke G, Dim M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using 0-hydroxy-0-methyl butyrate, glutamine and arginine: a randomized, double blind, placebo-controlled study. JPEN 2000;24: 133-9 Klein S, Simes J, Blackburn G. Total parenteral nutrition and cancer clinical trials. Cancer 1986;58:

McGeer AJ, Detsky AS, O’Rourke KO. Parenteral nutrition in cancer patients undergoing chemotherapy: a meta-analysis. Nutrition 1990;6:233-40 American College of Physicians. Parenteral nutrition in patients receiving cancer chemotherapy: a meta-analysis [position paper]. Ann Intern Med 1989;l 10:734 Klein S, Koretz RL. Nutrition support in patients with cancer: what do the data really show? Nutrition in Clinical Practice 1994;9:91-100 Foster KJ, Brown MS, Alberti GMM, et al. The metabolic effects of abdominal irradiation in man with and without dietary therapy with an elemental diet. Clin Radio1 1980;31:13-7 Bounous G, LeBel E, Shuster J, et al. Dietary pro- tection during radiation therapy. Strahlentherapie

Weisdorf S, Lysne J, Wind D, et al. Influence of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation. Trans- plantation 1987;43:833-8 Szeluga DJ, Stuart RK, Brookmeyer R, et al. Nutri- tional support of bone marrow transplant recipi- ents: a prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program. Cancer Res 1987;47:3309-16 Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. Ann Intern Med 19923 16:821-8 Schloerb PR, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications: a randomized double blind study. JPEN 1993;l 7:407-13 Charuhas PN, Fosberg KL, Bruemmer B, et al. A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation. JPEN 1997;21:157-61 Howard L, Ament M, Fleming CR, et al. Current use and clinical outcome of home parenteral and enteral nutrition therapies in the United States. Gas- troenterology 1995;109:355-65 Buchman AL, Ament ME, Dubin M, et al. Intrave- nous choline supplementation reverses TPN-associated liver disease. Gastroenterology 2000; 11 8(suppl 2):A852 Byrne T, Persinger RL, Young LS, et al. A new treatment for patients with short bowel syndrome. Ann Surg 1995;222:243-55 Scolapio JS, Camilleri M, Fleming CR, et al. Effect of growth hormone, glutamine, and diet on adapta-

1378-86

1975;149:476-83

288 Nutrition Reviews@, Vol. 58, No. 9

58.

59.

60.

61.

62.

63.

64.

65.

66.

tion in short-bowel syndrome: a randomized, controlled study. Gastroenterology 1997;113:1074-81 Griffiths AM, Ohalsson A, Sherman PM, et al. Meta- analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology

Trallori MA, D’Albasio GD, Milla M, et al. Defined- formula diets versus steroids in the treatment of active Crohn’s disease. Scand J Gastroenterol

Fernandez-Banares F, Cabre E, Esteve-Comas M, et al. How effective is enteral nutrition in inducing clinical remission in active Crohn’s disease?: a meta-analysis of the randomized clinical trials.

Riordan AM, Hunter JO, Cowan RE, et al. Treat- ment of active Crohn’s disease by exclusion diet: East Anglian multicenter controlled trial. Lancet

Greenberg GR, Fleming CR, Jeejeebhoy KN, et al. Controlled trial of bowel rest and nutritional support in the management of Crohn’s disease. Gut

Wright RA, Adler EC. Peripheral parenteral nutrition is no better than enteral nutrition in a p t e ex- acerbation of Crohn’s disease: a prospective trial. J Clin Gastroenterol 1990;12:396-9 Lochs H. Has total bowel rest been a beneficial effect in the treatment of Crohn’s disease? Clin Nutr

Dickinson RJ, Ashton MG, Axon AT, et al. Controlled trial of intravenous hyperalimentation and total bowel rest as an adjunct to the routine therapy of acute colitis. Gastroenterology 1980;79:1199-204 Mclntyre PB, Powell-Tuck J, Wood SR, et al. Con- trolled trial of bowel rest in the treatment of severe

1 995; 1 08(4): 1 056-67

1996;31:267-72

JPEN 1995;19:356-61

1993;342:1131-4

1988;29(10):1309-15

1983;2:61-4

67.

68.

69.

70.

71.

72.

73.

74.

75.

acute colitis. Gut 1986;27:481-5 Gonzalez-Huix F, Fernandez-Banares F, Esteve- Comas M, et al. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis. Am J Gastroenterol 1993;88:227-32 Aiges H, Markowitz J, Rosa J, Daum F. Home noc- turnal supplemental nasogastric feedings in growth-retarded adolescents with Crohn’s disease. Gastroenterology 1989;97:905-10 Bradley EL 111. A clinically based classification system for acute pancreatitis. Summary of the Interna- tional Symposium on Acute Pancreatitis, Atlanta, GA, September 11 through 13, 1992. Arch Surg

Uomo G, Rabitti PG, Laccetti M, et al. Predictive evaluation of acute necrotizing pancreatitis: results of a prospective study. Presse Med 1995;24:263- 6 Sax HC, Warner BW, Talamini MA, et al. Early total parenteral nutrition in acute pancreatitis: lack of beneficial effects. Am J Surg 1987;153:117-24 Dickerson RN, Vebe KL, Mullen JL, et al. Resting energy expenditure in patients with pancreatitis. Crit Care Med 1991 ;19:484-90 Hernandez-Aranda JC, Gallo-Chico B, Ramirez- Barba EJ. Nutritional support in acute pancreatjtis: controlled clinical trial. Nutr Hosp 1996;11:160-6 Kalfarentzos F, Kehagias J, Mead N, et al. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 1997;84:1665-9 Silberman H, Dixon Np Eisenberg D. The safety and efficacy of a lipid-based system of parenteral nutrition in acute pancreatitis. Am J Gastroenterol 1977;77:494-7

1993;128:586-90

Nutrition Reviews”, Vol. 58, No. 9 289

Documents

Evidence Base for Specialized Nutrition Support