Nutritional support in surgical practice: Part II

REVIEW

Nutritional Support in Surgical Practice: Part II Michael M. Meguid, MD, PhD, FACS, Antonio C. Campos, MD, MS, William G. Hammond, MD, Syracuse,New York On admission, a group of high-risk patients who are potential candidates for surgery can be identified, in whom prompt initiation of preoperative enteral or parenteral nutrition may reduce postoperative morbidity and mortality irrespective of the nutritional status. Among these are patients with inflammatory bowel disease, gastrointestinal fistulas, and pancreatitis. Substantial nutritional support has little or no direct effect upon the pathogenesis of the disease, but the discontinuance of oral intake may well have a beneficial effect on the basic disease process. Thus, the provision of enteral or parenteral nutrition gives the patient an optimal opportunity to marshal host defenses in support of healing. In organ system failures, e.g., acute renal failure, liver failure, and pulmonary failure, appropriate nutritional support may assist the patient in coping with the abnormal intermediary metabolism resulting from such failure until satisfactory organ system function returns. F r o m this review, it seems reasonably clear that the initially malnourished patient is less able to successfully withstand the adverse effects of vigorous therapy and/or severe illness than is the well-nourished individual. Hence, correction of malnutrition, either before initiating therapy or concomitant with the treatment, is very likely to be beneficial.

Fromthe SurgicalMetabolismand NutritionLaboratory,Department of Surgery,UniversityHospital,State Universityof New York Health Science Center, Syracuse, New York. Supported in part by Grant AM36275 fromthe National Instituteof Arthritis, Diabetes,Digestive and KidneyDiseases, National Institutes of Health, Bethesda,Maryland, and an educationalgrant fromMead JohnsonNutrition Division, Evansville,Indiana. Requests for reprints should be addressedto Michael M. Meguid, MD, PhD, FACS,Departmentof Surgery,UniversityHospital,SUNY Health ScienceCenter, 750 East Adams Street, Syracuse,New York 13210. Manuscript submitted February 13, 1989,and acceptedJune 12, 1989.

ALIMENTARY SYSTEM DISORDERS Short bowel syndrome: In the pre-parenteral nutrition era, survival with short gut syndrome was noted only in several case study reports. Meyer [1] reported the 16year survival of a young man after extensive resection of the small and large intestines, whereas Kinney et al [2] described detailed balance studies in a young man whose entire jejunum, ileum, and ascending colon were removed because of necrosis secondary to mid-gut volv-ulus, leading to the evolution of a systemic, stepwise nutritional program useful in the subsequent care of other patients with major losses of small bowel function. These reports were the exceptions, because the then available methods for postoperative management of fluid and electrolyte losses and of nutritional needs led to either the patient's demise or continuous institutional care. The advent of parenteral nutrition did much to foster success during the stormy postoperative course of such patients since it facilitated long-term nutritional support while the residual intestine could undergo adaptive structural and functional changes, including small bowel dilatation, villous enlargement, epithelial cell hyperplasia, and enhanced absorption. T h e a d a p t i v e changes, their possible mechanism, and their management after the advent of parenteral nutrition are well described in the comprehensive review by Tilson [3]. In a collected review of 50 newborn infants who survived small bowel resection, Wilmore [4] identified the following factors that correlated with a successful outcome: length of remaining bowel, presence of an ileocecal valve, normal birth weight, successful operative therapy, and lack of associated anomalies. Survival after massive intestinal resection was related to the length of the remaining small bowel. All but one infant survived resection that left 38 to 75 cm of jejunum and ileum. Of 14 patients with 15 to 38 cm of small bowel remaining between the ligament of Treitz and an intact ileocecai valve, 7 patients survived. No survivors were reported after resections that left less than 15 cm of jejunum or ileum, and no infant without an intact ileocecal valve lived with less than 40 cm of small bowel. The effect of massive intestinal resection on growth and development is shown in Figure 1. An initial lag in body weight was noted by most during the first year of life, followed by an accelerated weight gain that placed most children within normal limits of weight distribution after the first year. Survival is possible in the neonatal period after 90% enterectomy (leaving 25 to 30 cm of small bowel), if the ileocecal valve remains intact. Longer residual segments are necessary if the ileocecal valve is removed, and small bowel resection of more than 85% of the intestine may jeopardize survival. The use of parenteral nutrition in short bowel syndrome may be temporary or permanent, depending upon the adaptation of the patient's remaining functional gut.

THE AMERICAN JOURNAL OF SURGERY VOLUME159 APRIL 1990 427

MEGUID ET AL

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4

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Figure 1. Body weight of infants after massive intestinal resection. Note the initial lag in the first year of life, followed by catchup weight gain and normal distribution. Three Iinea represent the 10th, 50th, and 90th percentiles of body weight. Reproduced with permission from [4].

However, nutritional care remains of life-long concern, as demonstrated by Woolf et al [5], who studied eight clinically stable patients who were at least one year after bowel resection for inflammatory bowel disease (n = 5) or superior mesenteric artery thrombosis (n = 3) resulting in short bowel. The purpose of the study was to assess the nutritional requirements by evaluating the effect of different dietary and fluid intakes on calorie and divalent cation absorption for a 10-day period. In eight patients, the duodenum was intact; in four, the jejunum was present, and in the remaining four, only 112 cm of the jejunum were present. None had any ileum; five had no colon or rectum. Caloric balance was measured, and differences in the absorption of different caloric sources were determined. The diet chosen was lactosefree, with a low fiber content and contained 22% of total calories as protein, 32% as carbohydrate, and 46% as fat. Total fluid volume was kept constant, and all patients were in positive nitrogen balance. During a 10-day period, blood chemical concentrations, stool and/or ostomy volume, urine volume, electrolyte excretion, and calorie and divalent cation absorption were measured. In these patients, the absorptions of fat, carbohydrate, protein, and total calories were 54%, 61%, 81%, and 62%, respectively. Similarly, the absorption of the divalent cations calcium, magnesium, and Zinc were 32%, 34%, and 15%, respectively. These results suggest that patients with short bowel syndrome whose condition has been stable for at least 1 year and who can tolerate oral diets do not need to restrict 428

THE A M E R I C A N J O U R N A L O F S U R G E R Y

fat or to separate fluids from solids during their meals. Furthermore, they should increase their oral intake to 35 to 40 kcal/kg ideal body weight in order to ingest enough to counteract their incomplete absorption. The diet should contain 80 to 100 g protein/day in order to maintain a positive nitrogen balance with a large margin of safety. In addition, these patients may need oral supplementation of calcium, magnesium, and zinc to maintain divalent cation balance. The significance of this report is not only that a group of investigators could collect eight patients who were free of active disease and were nutritionally and metabolically stable, but that, with the assistance of parenteral nutrition, these patients survived the critical and often stormy initial postoperative course after massive enterectomy to achieve their long-term stability. Today, patients with functional or anatomic short bowel syndrome are expected to lead a relatively normal and productive life, with an estimated 14,300 patients receiving home parenteral nutrition and 260,000 patients receiving home enteral nutrition in the United States (OASIS Home Nutritional Support Patient Registry, Oley Foundation, Albany, NY; 1987). The long-term efficacy of this treatment modality, however, remains to be determined, since relatively few patients have been maintained exclusively on parenteral nutrition for more than 5 years. Nonspecifie inflammatory bowel disease: Early retrospective reviews have hinted at a high incidence of malnutrition using criteria of acute weight loss (greater than 10%), albumin (less than 3.0 g/dL), and transferrin. The frequency of malnutrition was 33% for Crohn's disease (regional enteritis -- 36% and granulomatous colitis = 29%) and 72% for ulcerative colitis in the study by Reilley et al [6], and 48% in Crohn's and 58% in ulcerative colitis in the study by Mullen et al [7]. The high incidence of malnutrition in these series seems due tO the fact that patients initially referred for parenteral nutrition often were those in whom conventional treatment had failed; they were critically ill and were being referred for parenteral nutrition as a last resort. Chronic undernourishment, however, is probably more common in Crohn's disease than in ulcerative colitis. Although overt weight loss is one of the most striking features of active inflammatory bowel disease, many other nutritional disturbances also occur. These may include reduced levels of serum albumin, pre-albumin, ferritin, calcium, vitamin D, hemoglobin (due to vitamin B 12, iron, and folic acid deficiency), urine creatinine excretion, peripheral blood lymphocyte count (including T-cells), fat and fat-soluble vitamins, potassium, magnesium, and zinc. Because restricting oral intake for bowel rest is part of standard therapy for inflammatory bowel disease, further weight loss often occurs. Indeed, prior to adequate therapy, diminished food intake from loss of appetite, protein losses from inflammed bowel wall, chronic blood loss and malabsorption from intrinsic bowel disease, and drugnutrient interactions produce further weight loss, anemia, and hypoproteinemia.

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Despite the high incidence of malnutrition in patients with inflammatory bowel disease, the role of nutritional support in the management of ulcerative colitis and Crohn's disease is still unclear. It is known that patients gain weight and improve their biochemical indices following adequate nutritional support. However, it is not clear whether reversal of malnutrition will reduce the need for surgical treatment with its associated morbidity and mortality. The data of Higgens et al [8] suggest that preoperative weight loss does not seem to adversely affect postoperative outcome. It is also not clear whether bowel rest from parenteral nutrition will enhance healing of the intestinal lesions of inflammatory bowel disease. Three randomized prospective studies were done to assess whether parenteral nutrition together with total bowel rest were primarily or only supportive therapy in inflammatory bowel disease. In the first study, Dickinson et al [9] prospectively randomized 36 patients (27 with ulcerative colitis and 9 with Crohn's disease) to either parenteral nutrition and total bowel rest (n -- 19) or to a control group (n = 17). Parenteral nutrition consisted of 2,000 to 3,000 m L / d a y of dextrose/amino acid solution with electrolytes and vitamins. The control group had a normal hospital diet ad libitum and no intravenous nutrients or vitamins except for blood and albumin. All patients had bed rest and 40 mg prednisone per day. The endpoints of the trial were either when prednisone could be reduced to 10 rag/day or when patients required operation. Response to therapy occurred in 65% of the control group, but 35% failed to respond to therapy and required operation. Of the parenteral nutrition group, 53% responded to nonoperative therapy in a mean time of 21 days, but operations were required in 47%. These data were interpreted to show that parenteral nutrition (of this magnitude) plus total bowel rest had no additional primary therapeutic effect on ulcerative colitis, beyond that provided by prednisone. Because of the small number of patients with Crohn's disease, no significant conclusions could be reached concerning the use of parenteral nutrition in Crohn's disease. In the second trial study, Mclntyre et al [10] studied 47 patients with severe acute noninfective colitis deemed severe enough to warrant admission to hospital and to require intravenous prednisolone therapy. Disease stratification on entry into the study was not undertaken because it was believed to be unreliable in distinguishing between ulcerative colitis and Crohn's colitis in acutely ill patients. A final diagnosis was made only after radiologic and pathologic data were finally available at the end of the hospital stay. Based on these data, 27 patients had ulcerative colitis, 16 had Crohn's colitis, and 4 had indeterminate colitis. All patients received intravenous prednisolone throughout the trial and were randomized to receive either parenteral nutrition (2,200 kcal, ranging from 1,400 to 2,950 kcal/day) and bowel rest or oral diet (1,800 kcal, ranging from 1,200 to 2,700 kcal/day). Patients were assessed every 7 days while hospitalized and followed up for a mean of 43 months. Outcome during hospitalization showed that remission was obtained in

59% of patients in the parenteral nutrition group and 60% of patients in the oral diet group. However, when outcome was analyzed according to the final pathologic diagnosis, significant differences were found between patients with ulcerative colitis and those with Crohn's disease. Surgical treatment was required in 14 of 27 patients with ulcerative colitis but in none of the 16 patients with Crohn's colitis. The data show that acute attacks of Crohn's colitis are much more likely to respond to parenteral nutrition plus bowel rest than are acute attacks of ulcerative colitis. In the third prospective study of Crohn's disease, Muller et al [11] examined the effect of parenteral nutrition as the sole therapy in 30 patients with acute Crohn's disease, admitted because of failed medical therapy of at least 3 years' duration or because they had developed complications (enterocutaneous fistulas, intermittent ileus, or bleeding) secondary to Crohn's disease. After admission, all other medications were stopped, and a Silastic catheter was inserted. Patients remained hospitalized at bed rest, during the acute phase, receiving parenteral nutrition (glucose/fat and amino acids; 45 keal/kg/ day) and total bowel rest. Once their clinical condition stabilized, patients were discharged; at home, they received parenteral nutrition for 10 to 12 hours overnight (30 kcal/kg/day) for 12 weeks. During this time, the patients were not allowed to eat or drink anything and received no other medications. After 12 weeks, parenteral nutrition was stopped, and an oral diet was started. Patients were subsequently followed every 6 months for 4 years. A cumulative recurrence rate of 60% occurred by 2 years and of 85% at 4 years. The cumulative recurrence rate after parenteral nutrition was fourfold higher than that after Crohn's disease in 56 patients during the 10year pre-parenteral nutrition era. However, sufficient data were not provided to satisfactorily evaluate the comparability of the retrospective historic control group, nor did the authors provide any data to correlate the initial reason for admission and therapy with the eventual outcome, except that high-grade stenosis at sites of previous anastomoses did not regress during parenteral nutrition. From this study, the authors concluded that parenteral nutrition was not a valid alternative to resection in the treatment of complications of Crohn's disease, although their data are incomplete and far from conclusive. An additional question is relevant, however. Would parenteral nutrition given preoperatively diminish the incidence of postoperative complications in a population wherein the frequency of preoperative malnutrition is recognized to be high? To address this question, Rombeau et al [12] reviewed the records of 33 consecutive patients who underwent operation for inflammatory bowel disease. Patients who did not receive or who got less than 5 days of parenteral nutrition were placed into Group 1, whereas those who received parenteral nutrition (44 kcal and 0.3 g nitrogen/kg/day; calories were provided as 80% glucose and 20% fat) for at least 5 days Preoperatively constituted Group 2. Patients who received preoperative parenteral nutri-

THE AMERICAN JOURNAL OF SURGERY VOLUME159 APRIL 1990 4029

MEGUID ET AL

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tion for at least 5 days had significantly fewer postoperative complications than those who did not, although both groups received comparable and significant amounts of parenteral nutrition after operation. As experience has shown, these favorable results from a retrospective review might well not hold up when subjected to a randomized prospective study, but the differences in the duration of preoperative parenteral nutrition are substantial, as are the differences in complications. Benefits similar to those bestowed by parenteral nutrition for the primary therapy of Crohn's disease have been claimed for enteral nutrition by Rocchio et al [13] and Axelsson and Jarnum [14]. Harries et al [15] examined this concept in a randomized controlled trial published in 1983. Thirty-five malnourished patients (criteria included anthropometrics, creatinine-height index, serum albumin levels, and T-cell counts) with active but uncomplicated Crohn's disease (criteria: clinical index score and serum orosomucoid levels) were randomized in a controlled cross-over study to examine the effects of a lowresidue liquid supplement (Ensure-Plus| , Ross Laboratories, Columbus, OH) on nutritional status and disease activity while continuing with conventional medical therapy. Group 1 received an ordinary diet that was given for 2 months (control period) followed by 2 months of the same diet with the additional supplements of the lowresidue preparation (treatment period). In Group 2, the order of dietary periods was reversed. The aim was to supplement each patient's diet to approximately 3,000 kcal/day. Patients in both groups continued to receive their pre-study regimens of either prednisolone or sulfasalazine and were assessed monthly. Seventeen percent of the study group were unable to take the nutritional supplement, so only 28 patients completed the study. Caloric intake was significantly higher during the 2-month treatment periods than during the control period for both groups. From the supplemental treatment, nutritional status was improved in both 430

groups, while serum orosomucoid levels dropped significantly. This latter finding suggested that disease activity was reduced. However, no further data were provided regarding the level of activity of the basic disorder, Whether such improvement could be maintained with a longer period of nutritional support or in patients with more severe disease remains unknown. Although nutritional support was often included in the management of Crohn's disease because the patients were poorly nourished due to reduced food intake and hypercatabolism, an additional rationale for parenteral nutrition was its use to induce remissions since it "rests the bowel." In this regard, O'Morain et al [16] postulated that Crohn's disease consisted of two main components: (1) an underlying predisposition of the gut to ulceration, and (2) a secondary local immunologic reaction to the passage of large amounts of foreign protein through the damaged gut wall. To test these notions, in a novel study, they attempted to treat this secondary aspect by allocating at random 21 patients with active Crohn's disease to either prednisone 0.75 mg/kg/day (n = 10) or to oral Vivonex| (n = 11) (40 to 60 kcal/kg and 8 to 21 g nitrogen/day) (Norwich Eaton Laboratories, Norwich, NY). After 4 weeks, normal food was gradually reintroduced to those who had received the Vivonex| regimen. The dietary regimens for those receiving prednisone was not specified. Clinical symptoms and laboratory values were assessed before treatment and at weekly intervals for 4 weeks and than at 3 months. Response to treatment was monitored by a simple activity index. Eight of 10 steroid-treated and 9 of 11 dietetically treated patients were considered to be in remission at 4 weeks and at 3 months (Figure 2). Treatment was considered to have failed in one patient in each group. In two separate multicenter trials, Summers et al [17] in 1979 in the United States and Malchow et a! [18] in 1984 in Europe reported that oral prednisone was the most beneficial overall treatment for Crohn's disease. Saverymuttu et al [19] compared this conventional therapy for Crohn's disease to the O'Morain et ars regimen of Vivonex | which is designed to remove antigens from the gut lumen. Thirty-seven patients with moderately active Crohn's disease were randomly assigned to prednisolone 0.5 mg/kg/day plus a normal diet or to an elemental diet (Vivonex| 1,800 to 2,400 kcal/day via nasogastric tube) plus several nonabsorbable oral antibiotics. The Crohn's Disease Activity Index (CDAI) and fecal leukocyte excretion were measured at admission and after 10 days of treatment. Fifteen of the 16 patients receiving Vivonex| plus nonabsorbable antibiotics and all 16 patients receiving prednisolone plus a normal diet improved clinically and exhibited significant reductions in the CDAI and fecal leukocyte excretion; differences in these values were not statistically significant between the two treatment arms. The authors concluded that decreasing the intraluminal concentration of bacteria and complex food molecules was associated with a rapid decrease in the activity of Crohn's disease. They suggested that these intraluminal factors play a role in initiating and maintaining inflammation and that their removal or alteration offers an approach to management different

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from, but equally effective as, suppression of the immunologic reaction by steroids. By inference, the use of parenteral nutrition instead of elemental enteral nutrition would also be beneficial for the same reasons. Improvement in general nutritional status is unlikely to be responsible for alleviating the symptoms of Crohn's disease, because clinical improvement from effective dietary regimens starts long before positive nitrogen balance develops. Winitz et al [20] and Bounous et al [21] documented altered gut bacterial flora in patients taking an elemental diet; this change might be responsible for the beneficial effects. Alternatively, the nitrogen source in Vivonex| is simple amino acids in which the concentration of glutamine is very high. In view of the numerous recent studies that show selective uptake of glutamine by enterocytes of the small intestine, exceeding the uptake of any other amino acids, and preferential metabolism of glutamine, it is conceivable that this aspect of the elemental diet Vivonex TEN | is responsible for its therapeutic beneficial effectl Other liquid diets contain peptides with variable-length chains and all contain some oligopeptides; any or all of these may be allergenic. Vivonex TEN | may thus be beneficial in one of two ways: (1) as the components of this diet are absorbed mainly in the upper small bowel, it may act simply to keep the dietary contents and digestive enzymes from gaining access to the more distal inflammed ulcerated gut; or (2) the secondary immune response to exogenous protein that gains access to the gut wall through the ulcerated mucosa may be decreased when the gut content of peptides is markedly reduced. In either case, Vivonex TEN | treatment for acute exacerbations of Crohn's disease offers a therapeutically effective and non-hazardous alternative to steroid or surgical therapy. Enteroeutaneous fistulas: In the 1960 landmark study by Edmunds et al [22], 53% of the patients with gastric or duodenal fistulas, 74% with jejunal or ileal fistulas, and 20% with large bowel fistulas were malnourished; the overall mortality rates (with and without definitive therapy) were 62%, 59%, and 64%, respectively. Four years later, Chapman et al [23] emphasized the benefits of nutritional support in the management and outcome of patients with enterocutaneous fistulas. In 56 patients, one third received optimal nutritional support, defined as greater than 3,000 calories/day as intravenous protein hydrolysates and dextrose, as part of their treatment, plus tube or oral feedings or both. Patients were in positive nitrogen balance. The other two thirds received suboptimal nutritional treatment defined as less than 1,000 calories/day, and they were in negative nitrogen balance. Patients receiving optimal nutritional support had a fistula closure rate of 89% and a mortality rate of 12%; with suboptimal nutritional support, these figures were 37% and 55%, respectively. Soeters et al [24], in a later series, reported the frequency of malnutrition in patients with fistulas to be 74%; a direct relationship between the volume of the fistula output and malnutrition was noted. Coutsoftides and Fazio [25] reported a 66% incidence of malnutrition in 174 patients with enterocutaneous fistulas of the jejunum and ileum. Malnutrition was defined

as a loss of at least 15% of ideal body weight; only 30% of the patients had serum albumin levels greater than 3.5 g/ dL, and 35% had less than 2.5 g/dL. In the presence of malnutrition, the overall mortality rate was 32%, whereas in its absence, it was only 4%. Whereas no patient with a serum albumin level greater than 3.5 g / d L died, the mortality rate was 42% in patients in whom the albumin level was less than 2.5 g/dL. From these data, it may be concluded that the frequency of malnutrition in patients with fistulas is high and appears to be related to the site and volume output of the fistula. However, whether malnutrition preceded or was consequent to fistula formation is not discernible from the data. Because of the high incidence of malnutrition in patients presenting with enterocutaneous fistulas, the use of nutritional support in these patients seems theoretically advantageous. Between 1973 and 1986, there were 10 reports concerning the experiences that investigators had. Table I summarizes their experience in the use of pareno teral and enteral nutrition in the management of 755 patients with 823 gastrointestinal fistulas of a variety of origins [24,26-34]. All were retrospective studies. From these studies, it can be concluded that most fistulas occurred after surgery for inflammatory bowel disease, cancer, diverticulitis, or trauma. In the majority, nutritional support was relied upon to assist in fistula closure. In this setting, 62% closed "spontaneously," whereas 30% needed direct operative intervention to close the fistula. The mortality rate varied from 5% to 28% (mean 17%), although mortality was higher in severely malnourished patients (27.8%) than in well-nourished patients (6.7%). Given that the main thrust of these studies was to evaluate the usefulness of nutritional support, in only six studies was the quantity and the type of nutritional support mentioned! Based on the data in the literature and our current practice, the indications for the use of nutritional support have been summarized in Figure 3. The data so far show that the role of enteral or parenteral nutrition in fistula management is primarily supportive in nature: to treat malnutrition or prevent further deterioration of debilitated patients. However, could nutritional support, by decreasing or modifying the composition of gastrointestinal and pancreatic secretions, as suggested by the data of Hamilton et al [35], Stabile et al [36], and Dudrick et al [37], have a primary therapeutic role? To clearly answer this question, a randomized prospective study would need to be done, but given the heterogeneity of patients with enterocutaneous fistulas and the ethical concerns regarding an adequate control population, it is unlikely that this question can satisfactorily be answered. However, a number of investigators have addressed the issue of modifying gastrointestinal fistula output by nutritional or pharmacologic manipulations. In dogs during the administration of secretin and pancreozymin, Hamilton et al [35] reported a significant decrease of 50% in the volume of duodenal fluid by the administration of parenteral nutrition as 20% dextrose and 5% amino acids. They also observed that the bicarbonate concentration was increased, but no effect was observed on the volume or pepsin content of gastric secretion.

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MEGUID ET AL TABLE I

Summary of the Results of the Use of Nutritional Support in the Management of Gastrointestinal Fistulas Year, Author, Reference

No, of Patients/ Fistulas

Spontaneous/ Operative Closure

Overall Mortality (%)

Esophagus; gastro- IBD; cancer; EN duodenum; pseudocyst 3,000-5,000 small intestine; pancreas; 15: kcal/day; colon; pancreounderlying elemental diet; biliary disease; 21: hydrolysated postoperative casein Gastro-duodenum; IBD: 23%; cancer: PN small intestine; 5%; surgical 2,000-5,000 colon (external injury: 15%; kcal/day; 80or internal) anastomotic 200 g AA day breadown: 24%

7 5 % / 7 % ; 3% remained open

28

37/37

Gastro-duodenum; small intestine; colon

5 8 % / 1 6 % ; 8% remained open

56/65

Esophagus; gastroduodenum; small intestine; colon; pancreobiliary

1973 Voitk et al [26]

29/36

1973 MacFadyen et

62/78

al [27]

1974 Rocchio et al

[28]

1975" Kaminsky et al

[29]

1978" Reber et al

128/128

Esophagus; gastro- IBD: 26%; duodenum; cancer: 22%; small intestine; diverticulitis: colon; pancreo12.5%; ulcer: biliary 9 %; other: 29% Lower esophagus; All postoperative gastroduodenum; small intestine

1981" Thomas et al [31]

42/42

1982 Sitges-Serra et

75/87

al [32] 114/132

[33]

1986 Rose et al [34]

Cancer: 30%; IBD: 27 %; postoperative: 86 %

Esophagus; gastro- Cancer: 20%; duodenum; irradiation: small intestine; 12%; IBD: 4%; colon; pancreospontaneous: biliary 8 %; postoperative: 92%

[24]

1984 Mclntyre et al

Causative Factors

104/104

[30]

1979" Soeters et al

Fistula Site

108/114

Type/Composition of Nutritional Support

PN + EN -- 65% PN = ? EN = Vivonex Codelid

7 0 % / 2 2 % ; 8% remained open

PN = 2,000-3,000 8 0 % / 1 1 % kcal/day 8055% 175 g AA/day or AA dextrose + lipids 3 g/kg/ day and/or 7% elemental diet: 30% PN = ? 35%/60% EN=?

16

12.5

22

62%/70%

21

PN = 2,800-3,500 7 1 % / 9 . 5 % kcal/day

26

Esophagus; gastro- All postoperative duodenum; small bowel; colon Small intestine; IBD: 42%; colon cancer: 21%; diverticulitis: 9 %; other: 28%

2,500-4,500 kcal/ 7 1 % / 1 4 % day; N/cal = 175:1; AA, dextrose, lipids AA; dextrose; 27%/62% lipids

21

Esophagus; Gastroduodenum; small intestine; colon; pancreobiliary

1,800-4,000 kcal/ 6 1 % / 2 5 % day; 25 % dextrose; 5% AA; lipids 2X weekly

14

IBD: 11%; diverticulitis: 10%; cancer: 6%; radiation: 6 % ; trauma: 7%

PN = ?

6.5

5.1

Comments Except cancer patients, mortality -16%

All patients with fistulas remaining open died -mortality = 14.2%; fistula output ~ 50% with PN 78% fistula output ~ with EN; except cancer patients, mortality = 6% Except cancer patients, mortality = 4%

78% deaths occurred in IBD, cancer, or previous abdominal operations; complications of PN = 28% Spontaneous closure with PN = 68%, without = 20%

Mortality and spontaneous closure compare favorably to earlier series at same institution No mortality in colonic fistulas

66% of patients were operated on; only 14% of colon fistulas closed spontaneously 51% patient complications due to PN

* Historic series of these studies not included in this table. PN = parenteral nutrition; EN = enteral nutrition; IBD = inflammatory bowel disease; AA = amino acid; Kcal = kilocalories; N = nitrogen; ,~ = decrease.

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Reber et al [30] reported that four patients with highoutput gastroduodenal fistulas (1,500 to 2,000 mL/24 hours), while receiving at least 3,000 kcal/day as parenteral nutrition, had a decrease in output to 300 to 800 mL/24 hours after cimetidine was given every 6 hours. DiCostanzo et al [38] treated 37 patients with external gastrointestinal fistulas by a combination of parenteral nutrition and somatostatin, which was continuously infused intravenously. Patients received 42.3 4- 5.5 kcal/ kg/day and between 150 to 200 kcal/g of nitrogen; fat emulsions constituted 50% of the non-protein energy supply. Fistula output dropped significantly after somatostatin was given in the first 2 days of treatment, as compared with non-treatment levels. The reduction of the fistula output was about 70% after the first day of treatment and reached 78% after the second day. However, no further significant reduction was seen in fistula output thereafter. Overall "spontaneous" closure was achieved in 82% of the cases. Overall mortality was 13%; all deaths occurred in patients who did not respond to the treatment with somatostatin. In the absence of a randomized controlled clinical trial, the mortality rates and the success rates in "spontaneous" fistula closures appear to be comparable. As noted earlier, an accurate evaluation of the effect of parenteral or enteral nutrition in reducing mortality and increasing rates of spontaneous closure of enterocutaneous fistulas is very difficult because of the lack of adequately controlled studies and the heterogeneity of the patients. Most studies are retrospective analyses of patients with fistulas; the results are usually compared with those obtained in historic control subjects treated before the use of parenteral nutrition. It must be again emphasized that other important non-nutritional achievements have been made in the last 20 years in the care of severely ill patients, including better management of acid-base and electrolyte balance, specific cardio-respiratory support, improved antibiotic therapy, and more intensive nursing care. The influence of these non-nutritional factors on outcome is also very difficult to quantitate and may be of equal importance. Acute panereatitis: Although the detailed pathogenesis of acute pancreatitis is not known, there are marked variations in severity, ranging from mild acute pancreatitis, which is easily managed with nasogastric suction, intravenous fluids, and general supportive care, to severe acute pancreatitis with serious cardiopulmonary and gastrointestinal complications and sepsis. Also, there have been varying criteria and standards for diagnosing the disease and categorizing its severity. Thus, the appropriately matched therapeutic responses have also been variable. Consequently, among the early articles concerning the use of nutritional support in pancreatitis (all nonrandomized trials) that we reviewed, it was difficult to compare results. However, in the study by Ranson et al [39], 11 criteria were established as having significant prognostic value. Of 79 patients with fewer than 3 of these signs, 2 died and 9 were seriously ill. By contrast, of 21 patients with 3 or more of these signs, 13 died and 7 were seriously ill. These 11 early objective criteria for the gravity of acute pancreatitis have been subsequently used

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/\

~

--"~ ] FistulaClose

4,

[

Good Surgical Risk [

Poor Surgical Risk

Figure 3. The role of nutritional support in gastrointestinal fistulas.

in categorizing patients for the evaluation of therapeutic nutritional modalities. The early reports of encouraging results with the use of either parenteral or enteral nutrition in pancreatitis are useful for understanding the evolution of the role of nutritional support in this condition. Ranson et al [39] demonstrated that in patients with acute pancreatitis in whom

THE AMERICANJOURNAL OF SURGERY VOLUME159 APRIL 1990 433

MEGUID ET AL

there is a nonfunctioning gastrointestinal tract, nutritional status could be maintained via nutritional support. Feller et al [40], in reviewing their management experience of 200 patients with severe pancreatitis in 1974, noted that 42% of the patients had profound nutritional depletion. Interestingly, although not objectively defined, this diagnosis was considered by the authors as a complication of acute pancreatitis. They concluded that in severely ill patients, the reduction in the overall mortality rate from 22% in a series of historical control subjects to 14% in the current series was attributable to nutritional support using a combination of parenteral and enteral nutrition. The degree to which nutritional depletion developed with acute pancreatitis was detailed by Blackburn et al [41] in 1976. Among 77 patients with varying types of pancreatitis, 13 (17%) were categorized as having severe protracted acute pancreatitis. All these 13 patients had significant malnutrition, as defined by anthropometrics, serum albumin levels, and lymphocyte status. The distribution of degrees of malnutrition among all 77 patients with pancreatitis did not significantly differ from that found in a prior survey of their hospital population with gastrointestinal disorders, but the patients with severe acute protracted pancreatitis were the most severely malnourished of all. In particular, these patients showed an especially marked loss of lean body mass. Eleven of the 13 patients with severe protracted acute pancreatitis survived. These had abscesses or pancreatic duct disease amenable to surgery; they received nutritional support with both parenteral and enteral nutrition via several modalities from 35 to 109 days (mean = 64 days). Improvement of their nutritional condition was shown by elevations in serum albumin, increased lymphocyte counts, and increases in the creatinine-height index. On the basis of these two studies, it was then reasonable to conclude that the improved results were caused in part by nutritional therapy. On the assumption (not yet well documented) that severe acute pancreatitis is associated with a hypermetabolic state, and given the usual inability of such patients to maintain dietary intake, parenteral nutrition has become part of standard therapy. The early optimism regarding the effect of nutritional support on outcome was continued in subsequent reviews. While accepting the concept that parenteral nutrition had no particular effect upon the acute disease process in the pancreas, Goodgame and Fischer [42] and Grant et al [43] both concluded that the use of parenteral nutrition (hypertonic glucose and amino acid) served two useful purposes: (1) it corrected nutritional abnormalities, and (2) it maintained the nutritional status of patients unable to eat due to protracted gastrointestinal tract dysfunction due to the pancreatitis and its co-morbidities. Although the patients were not well characterized as regards the extent of disease, mortality rates in both studies reflected the fact that nutritional support permitted patients to survive in what would have otherwise been lethal circumstances. In an effort to answer the question as to whether early parenteral nutrition has a direct effect on the subsequent

clinical course of patients with acute pancreatitis, Sax et al [44] prospectively studied 54 patients with acute pancreatitis. They were randomized to receive either conventional therapy (intravenous fluids, antacids, and nasogastric suction) or parenteral nutrition therapy (25% glucose, 4.25% amino acids with 10% lipid infused twice weekly). Therapy in both groups was initiated within 24 hours of admission. In all cases, parenteral nutrition infusion rates were gradually advanced to estimated needs over 2 to 3 days. Those patients in the control arm who did not achieve an adequate oral intake by 7 days were crossed-over to parenteral nutrition. Nutritional assessment data were absent, as were any useful data regarding severity of disease, except that the mean number of Ranson's criteria was less than 2 in both groups. The results showed no difference between the control and parenteral nutrition groups in (1) the number of days to first oral intake or to solid diet, (2) duration of hospitalization, and (3) number of complications of pancreatitis. The authors concluded that there was no advantage in the use of early parenteral nutrition. Although this study was potentially useful, since it was a prospectively randomized clinical trial, the conclusions are flawed for the following reasons: (1) compared with the patients in the studies discussed earlier, and based on Ranson's criteria, these patients did not have severe pancreatitis, a view supported by the paucity of total complications, the low mortality rate, and the fact that 57% of patients were ingesting an adequate oral diet by 7 days; (2) the parenteral nutrition group did not reach adequate therapeutic levels of parenteral nutrition until day 3, suggesting that most patients only received adequate parenteral nutrition for 4 days; (3) the control group was switched to parenteral nutrition after 7 days, suggesting that the investigators believed that there was supportive benefit from parenteral nutrition; and (4) the endpoints for each group seemed to be different; because of social reasons, hospital stay is an unreliable endpoint, and no data were provided regarding recurrence of symptoms when patients resumed an oral intake. Because of the heterogeneous nature of the disease and the patients that incur it, it will be difficult to do a satisfactory randomized prospective study. Since there are ethical questions involved in withholding nutritional support from otherwise starving patients with severe acute pancreatitis, an adequate control group may not be possible. To date, the evidence indicates that parenteral nutrition most likely has no beneficial effect upon the pathogenetic process in the pancreas and therefore is not likely to be of significant benefit in the commoner mild or moderate forms of the disease, particularly if no surgical intervention is needed as part of the treatment. However, the evidence is most persuasive that, in severe and/or protracted acute pancreatitis, especially in alcoholic patients with an already compromised nutritional status, the prompt and vigorous use of parenteral nutrition may well be crucial for the survival of these severely ill patients with major metabolic disturbances, particularly if pancreatic complications ensue and/or operative measures are indicated. Because of the reported incidences (from 4.5% to

4~34~ THE AMERICAN JOURNAL OF SURGERY VOLUME 159 APRIL 1990

NUTRITIONALSUPPORT IN SURGICALPRACTICE

] []

GROUP A 9 etp < 0.005 ID p < 0.05 GROUP B

.(9,2) 600

S00

600

ooo

_z

400

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Figure 4. Biochemical values of patients with acute pancreatitis who survived (Group A) and who died (Group B) before discontinuation of the full extent of parenteral nutrition. Reproduced with permission from [48].

300

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200

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38%) by Dickson et al [45] and Cameron et al [46] of hyperlipidemia in patients with acute pancreatitis, it has been commonly believed that lipid abnormalities play a role in the pathogenesis of pancreatitis. Consequently, there is often reluctance to use lipids in parenteral nutrition. Silberman et al [47] studied 11 patients with acute pancreatitis of apparently moderate severity (although specific criteria were not provided) who received parenteral nutrition (glucose, amino acids, and 150 to 350 g of fat per day) for a mean of 11 days. Significant hypertriglyceridemia was not noted, but the customary progressive decrease in serum amylase levels was seen. The pancreatic process was neither aggravated nor exacerbated. They concluded that the use of lipids with parenteral nutrition had a salutary effect because (1) the nutritional status was maintained or improved, as shown by a positive nitrogen balance being achieved in each patient, and (2) no discernible effect on the pathologic process in the pancreas per se was noted. More recently, VanGossum et al [48] studied 18 patients with severe protracted acute pancreatitis who were given lipids with parenteral nutrition (30 kcal/kg/day, 34% to 70% of nonprotein calories as lipid, mean daily fat intake of 100 g) for a mean duration of 32 days. Clinical and biochemical data were compared between patients who survived and those who died. The mean sum of Ranson's criteria in patients who died was significantly higher than in those who survived (6.8 4- 1.2 versus 4.2 42.4). Persistent hypertriglyceridemia, hyperglycemia, hypoalbuminemia, and higher insulin requirements were observed toward the end of parenteral nutrition therapy in patients who died as compared with those who survived (Figure 4). This appeared to be related to more severe disease in those who died. In four patients, energy metabolism was studied in greater detail. The results (Table II) reflect the inability to utilize nonprotein energy in the patients who died (Patients 1 and 4). In these two patients, the measured ener-

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10

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gy expenditure was only 60% and 78% of the calories infused, whereas in the two who survived, 108% and 133% of the infused calories were oxidized. Since the total caloric intake and the basal energy expenditure predicted by the Harris-Benedict equation were comparable in the four patients, the data suggest that the patients who died were relatively hypometabolic and thus unable to oxidize an appropriate proportion of the infused calories. The cause of the observed hypertriglyceridemia could be either increased fat synthesis from hyperglycemia and high insulin infusions or reduced clearance of lipids. In three of the four patients in whom the respiratory quotient was measured, fat oxidation was almost as good as carbohydrate oxidation, findings that are comparable to those observed by Roulet et al [49] in other critically ill patients. Thus, at least in these three patients, reduced fat oxidation probably did not contribute to the hypertriglyceridemia observed. Furthermore, there was no correlation between the proportion of lipid calories infused and plasma triglyceride levels. The data suggest that the observed hypertriglyceridemia was not due to a specific abnormality of fat metabolism, but rather that it is part of an illness-related global abnormality of energy metabolism that includes hyperglycemia and increased insulin requirements in attempts to control it. Buch et al [50] prospectively studied 117 patients with acute pancreatitis: 68% had normal serum lipid levels, 24% had varying hyperlipidemic levels, and only 8% had constant hyper!ipidemia (Ranson's criteria were not given). Fat tolerance tests were done in 25 patients during an acute attack of pancreatitis and in 11 control subjects. The investigators also measured post-heparin lipolytic activity after injecting 60 IU heparin per kg body weight. According to the intravenous fat tolerance tests, the hyperlipidemic patients did not show an impaired turnover of triglycerides. The elimination coefficients were 3.5 in the 13 normolipidemic patients with pancreatitis, 4.4 in the 12 hyperlipidemic patients with pancreatitis, and 4.3 in the 11 control subjects, values that were not

THE AMERICAN JOURNALOF SURGERY VOLUME159 APRIL1990 435

MEGUID ET AL

TABLE II

Energy Metabolism in Four Patients with Severe Acute Pancreatitls*

Patient/ Outcome

HBEE

1/Died 2/Survived 3/Survived 4/Died

1,451 1,620 1,892 1,787

AEE

NonProtein RQ

Calorie Intake

Oxidation

% Intake Oxidized

CHO

Lipid

CHO

Lipid

CHO

Lipid

1,489 2,342 2,880 1,607

0.79 0.90 0.71 0.84

633 1,298 996 802

1 626 865 1.168 1,252

417 1,428 29 739

1,972 736 2.851 868

66 110 35 92

66 85 244 69

9 Adapted with permission from [48]. HBEE = Harris-Benedict energy expenditure; AEE = actual energy expenditure; RQ = respiratory quotient; CHO = carbohydrate.

TABLE III

Pancreatic Secretions with Enteral Feeding* Enteral Solution

Total Volume

% Change

Nitrogen (g/L)

% Change

Amylase (U/liter)

% Change

Lipase (U/L)

% Change

HCO3 (mEq/L)

% Change

Baseline TPN Polycose (50 mL/hr) Vivonex HN (50 mL/hr) Criticare HN (50 mL/hr) Osmolite (50 mL/hr)

1,350 700 1,720 1,350 1,250

--48 +27 0 --7

1.34 2.33 1.73 2.00 2.26

74 29 49 69

23,813 5,819 9,045 17,803 3,711

-75 --62 --25 --84

1,800 15,500 82,100 22,500 384,900

761 4,461 1,317 21 283

214 145 163 169 75

--32 --24 --21 --65

9 Reproduced with permission from [52]. HCO3 = bicarbonate.

significantly different. Despite the high dosage of triglycerides used, no pancreatitis or other adverse reactions were provoked. Total post-heparin lipolytic activity was similar in the normolipidemic and hyperlipidemic patients, but the hepatic fraction was significantly decreased in the hyperlipidemic patients. Thus, no defect in triglyceride turnover was demonstrated, and the authors justly concluded that the observed increases in the serum triglyceride level with pancreatitis were due to increased synthesis or mobilization. Taken together, these data indicate that most hyperlipidemia seen in association with pancreatitis are related to metabolic abnormalities secondary to the illness, rather than as a primary causative factor. Further, the addition of lipid to the parenteral nutrition regimen seems to be without danger as regards exacerbation of the disease process. Finally, persistent hyperlipidemia during a protracted course of severe pancreatitis (in the absence of known congenital hyperlipidemias) may have an ominous prognostic impact. Pancreatic fistulas: When parenteral nutrition is given and oral intake discontinued, the secretions of the gastrointestinal tract decrease, and, later, the mass of the gastrointestinal tract reduces, thereby placing the gut at functional rest. Hence, parenteral nutrition has been proposed as adjuvant therapy in severe acute pancreatitis, not only to provide nutritional support but to place both the gastrointestinal tract and the pancreas at rest, thereby potentially decreasing complications. In a single patient with a pure pancreatic fistula studied by Bivins et al [51], parenteral nutrition (10% to 25% glucose, 3.5% amino acids, and 10% lipids) was not associated with increases in fistula volume or protein output, whereas oral protein and 436

THE AMERICAN JOURNAL OFSURGERY

fat caused rapid increases in pancreatic exocrine output. In a similar study, Grant et al [52] noted the effects on pancreatic exocrine function of various enteral nutrient products delivered via the jejunum. Results are shown in Table III. Feeding via a jejunostomy catheter distal to the duodenum bypassed the upper gastrointestinal tract. This avoided the cephalic phase of eating, decreased secretions due to decreased vagal stimulation, reduced gastric acid secretion, and caused less stimulation of secretin and pancreozymin. Because these proximal effects of oral feeding were avoided, pancreatic exocrine function was also decreased. A reduction in the output of pancreatic exocrine juice through a fistula can foster its spontaneous closure; it may also decrease nutritional demands and metabolic complications. To discover whether time to closure could be shortened by giving active suppressants of secretin in addition to parenteral nutrition, Pederzoli et al [53] gave parenteral nutrition alone (n = 18) or parenteral nutrition combined with continuous intravenous infusion of drugs capable of inhibiting pancreatic secretion (i.e., somatostatin In = 8], calcitonin [n -- 7], or glucagon [n = 12]) to 45 patients with high-output pancreatic fistulas. Parenteral nutrition consisted of glucose and amino acids (no fat) with appropriate electrolytes, providing an average of 33 kcal/kg in well-nourished patients and up to 50 kcal/kg in malnourished patients. There was no difference in body weight or nutritional status (criteria not stated) between the patients at the beginning of or during treatment. Four schedules were used. Figure 5 shows the progress of fistula closures observed in each group over time. A slow and moderate reduction in the mean fistula output occurred with the three treatments: parenteral

VOLUME 159

APRIL 1990

NUTRITIONALSUPPORTIN SURGICALPRACTICE

CLOSURE

,oo.~ 0080?OeOS0403020-

Figure 5. Percentage and time of closure of pancreatic fistulas treated with four different treatment schedules, as indicated in the key. Reproduced with permission from [53].

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nutrition alone, -39%; parenteral nutrition + glucagon, -45%; and parenteral nutrition + calcitonin, -51%. Parenteral nutrition plus somatostatin was followed by a marked decrease of 82% in the fistula output within 24 hours and subsequent rapid closure. Although the report does not indicate the criteria used to select the treatment regimen for each patient (this was not a randomized trial), 93% of all fistulas closed without requiring operation. Although there was no significant difference in closure rate among the four regimens, parentera! nutrition plus somatostatin induced closure in a much shorter time (mean: 7 4- 3 days) than did the other regimens. This difference is highly significant. Most assuredly, this potentially valuable observation is worthy of further study for confirmation. ORGAN SYSTEM FAILURE Acute renal failure: The development of hypercatabolic acute renal failure (serum creatinine greater than 3 m g / d L for 2 or more consecutive days) after surgery or severe trauma or occurring in a setting of multiple organ failure, with or without sepsis, is still associated with a 45% to 50% mortality rate [54]. In acute renal failure, the requirements for protein and amino acid [55], as well as those for energy [56], are increased. Frequent dialysis causes even greater hypermetabolism; the increase in energy expenditure during dialysis is superimposed on a metabolic rate that in most cases is already elevated. Mault et al [57] measured resting energy expenditure in 29 patients with acute renal failure and found it to be 20% to 50% above normal. In a retrospective study over 22 years of 352 patients with acute renal failure, Rainford [54] observed a significant increase in survival between the periods 1958 to 1964 (48% survival), 1965 to 1975 (58% survival), and 1976 to 1980 (71% survival). In examining the variables that changed during these periods, Rainford found that the average caloric intake during these periods correlated

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with the increasing survival rates (1958 to 1964 less than 1,000 kcal/day; 1965 to 1975 less than 2,000 kcal/day; and 1976 to 1980 approximately 3,000 kcal/day). He speculated that the administration of hypercaloric parenteral nutrition contributed significantly to the increased survival of these patients. Early studies by Wilmore and Dudrick [58] and Abel et al [59] suggested that patients with acute renal failure would benefit from treatment with a parenteral nutrition solution consisting of glucose and small quantities of eight essential amino acids (EAA). The rationale was derived from the work of Giordano [60] who showed that administration of EAA decreased urea production and enhanced urea re-utilization, thereby decreasing the accumulation of potentially toxic nitrogenous metabolites. The first prospective double-blind study of Abel et al [59] compared the provision of parenteral nutrition (glucose + 8 EAA) or isocaloric quantities of hypertonic glucose alone to a total of 53 patients with acute renal failure. In both groups, caloric support of 1,200 to 3,000 kcal/day was administered arbitrarily depending on each patient's water balance and glucose tolerance. Seventyfive percent of patients recovered when given glucose with EAA, whereas 44% recovery occurred with glucose alone. The data of Abel et al [61] and, subsequently, those of Toback [62] suggest that the infusion of amino acids was associated with a shortened duration of acute renal failure; moreover, blood urea nitrogen, magnesium, potassium, and phosphorous levels either stabilized or decreased, which, in turn, led to less need for dialysis and eventually to improved survival. Leonard et al [63] carried out a randomized prospective trial in which patients with acute renal failure were given either intravenous glucose and EAA or glucose alone. They observed no improvement in recovery of renal function, in survival, or in the degree of wasting. Feinstein et al [64], in a controlled double-blind study, compared intravenous treatments of glucose alone, glucose With

THE AMERICAN JOURNAL OFSURGERY VOLUME15~ APRIL1990 437

MEGUID ET AL

TABLE IV Prevalence of Malnutrition in Chronic Liver Disease as Related to Histologic Diagnosis and Severity of Disease*

Classification of Malnutrition

Histologic Diagnosis Noncirrhosis Cirrhosis (n = 60) (n = 81)

Abnormal but not diagnostic Kwashiorkor-like Marasmus Both kwashiorkor and marasmus

Mild (n = 129)

Severity of Disease Moderate (n = 83)

Severe (n = 72)

51.7

43.2

50.4

25.3

13.9

0 41.7 6.7

8.6 17.3 30.9

2.3 42.6 4.6

13.3 14.5 47.0

8,3 5.6 72.2

Adapted with permission from [65].

EAA, or glucose with EAA and non-essential amino acids (NEAA), with the rationale that a mixture of EAA and NEAA would promote better recovery than EAA alone. No significant difference in recovery of renal function or survival was seen between patients receiving glucose alone, glucose and EAA, or glucose and EAA and NEAA. Although the previously described three studies [58,59,61] have suggested that patients with acute renal failure may benefit from treatment with infusions of glucose and small quantities of EAA, other studies have also shown that treatment of acute renal failure with varying quantities and types of intravenous parenteral amino acids does not seem to cause dramatic improvement in either the severity of the catabolic response, the rate of renal functional recovery, or eventual survival, unless the patient is in positive energy balance. This is in keeping with the results of a study by Bartlett et al [56], which showed that overall survival in critical illness correlates with the degree of positive energy balance, expressed as cumulative caloric balance. Chronic liver disease and hepatic eneephalopathy: Mendenhall et al [65] performed a complete nutritional assessment in 284 patients with alcoholic liver disease. The observed nutritional changes were classified into those associated with marasmus or those characterized as related to kwashiorkor. A smaller group of 21 alcoholic patients without clinical evidence of liver disease were also studied. All the indices used to measure malnutrition increased in prevalence as the severity of liver disease increased. None of the patients with liver disease was completely free from malnutrition. Even 62% of alcoholic patients without liver disease showed abnormalities. In patients with alcoholic hepatitis, some findings associated with marasmus were seen in 86% and some features of kwashiorkor were observed in 100%--these features correlated closely with the clinical severity of the liver disease (Table IV). Recognition that malnutrition appeared to precede the development of liver injury is important so that appropriate nutritional therapy can be provided. Although malnutrition in liver disease is associated with increased morbidity and mortality, therapeutic dilemmas are posed by attempts at feeding these critically ill patients via parenteral nutrition because of their relative intolerance to water, sodium, and protein due to their ascites and encephalopathy, or by enteral nutrition because of anorexia and malabsorption. 438

THE AMERICAN JOURNAL OF SURGERY

In the mid-1970s, Fischer et al [66,67] used a liver disease-specific amino-acid parenteral nutrition solution enriched in branched-chain amino acids (BCAAs) and low in aromatic amino acids (AAAs) and methionine in patients with hepatic encephalopathy; this amino-acid mixture was given with hypertonic glucose. The rationale for this form of disease.specific parenteral nutrition solution was as follows: chronically elevated circulating plasma AAAs are seen in protein calorie malnutrition, due to the breakdown of skeletal muscle mass. BCAAs compete with AAAs for the same transport mechanism across the blood-brain barrier. In the presence of hepatic failure, the AAAs are not catabolized, whereas the BCAAs are preferentially catabolized by skeletal muscle for energy, thereby decreasing the ratio of BCAAs:AAAs in circulating plasma and consequently facilitating the preferential uptake of AAAs across the blood-brain barrier. The infusion of BCAA-enriched solutions provides energy and stimulates protein synthesis with a resultant decrease in plasma AAAs. This latter decreases AAA uptake across the blood-brain barrier; the lower AAA levels in plasma, brain, and cerebral spinal fluid result in a more normal aminergic neurotransmitter profile. In patients with hepatic encephalopathy, infusion therapy with such solutions in hypertonic glucose results in decreased hepat]c encepha!opathy associated with normalization of the plasma amino acid profile and an improved BCAA:AAA ratio. Fischer et al [67] in 1976 showed that patients with hepatic encephalopathy from chronic hepatic failure, who are usually intolerant to the administration of amino acids, tolerated infusion of up to 125 g of a BCAAenriched solution. In many instances, increased arousal from hepatic encephalopathy, better nitrogen retention, and improved survival were noted. In the last few years, a number of randomized prospective trials have been reported by Rossi-Fanelli et al [68], Cerra et al [69,70], Wahren et al [71], Strauss et al [72], Gluud et al [73], and Fiaceadori et al [74,75]. These trials differ in several aspects, including the patient population, the types of cirrhosis included, and the control treatment used. Nevertheless, the effects on hepatic encephalopathy and on survival in these studies can be considered in general. With the exception of the trial by Wahren et al [71] in which the major caloric supplement was derived from fat, in patients receiving BCAA, wakeup from hepatic encephalopathy was at least as good and

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NUTRITIONAL SUPPORT IN SURGICAL PRACTICE

TABLE V

Summary of the Results of the Use of Parenteral or Enteral Nutrition in Surgical Practice Indications Preoperative (PN)

Postoperative (PN or EN)

Cancer (PN)

Trauma (PN or EN)

Burns (PN or EN)

Pancreatitis (PN)

Inflammatory bowel disease (PN or EN)

Results

Author, Reference*

PN < 5 days ineffective in reducing postoperative complications; PN 5-7 days may be of benefit; PN 7-10 days effective in reducing postoperative complications and mortality PN effective in reducing hospital stay and promoting wound healing when used in malnourished patients. EN better than oral 1' nutritional parameters, ~ sepsis and hospital stay. EN elemental vs non-elemental equally effective. PN vs EN equally effective. Surgical treatment: PN effective in reducing major complications, infection, and mortality. Chemotherapy: PN has no Influence in survival rate or tumor response to therapy. Radiotherapy: PN has no influence in treament tolerance or survival rate. EN vs Oral: ~ sepsis and 1' nutritional parameters. EN vs PN: both equally effective. BCAA-enriched vs conventional PN: BCAA influences nutritional parameters, but not postoperative morbidity and mortality. Caloric source: Fat -I- glucose better than glucose alone carbon dioxide production glucose intolerance liver test abnormalities Supplementation of caloric intake by PN failed to improve outcome. Supplementation of calorie-protein needs by PN or EN: 1' immunoresistance 1' nutritional parameters t mortality Conflicting results in retrospective studies, PN ineffective in reducing hospital stay or complications. PN effective in inducing remission and avoiding surgery in Crohn's disease, but long-term remission lower than surgical treatment. EN effective in Crohn's diease. Preoperative PN for at least 5 days reduces postoperative complications.

Comments

Holter [55] Moghissi [57] Muller [56]; Bellantone Heatly [59]

[58];

Collins [61]; Preshaw [63] Sagar [64]; Yeung [66]; Moore [67]; Fick [65]; Adams [68]; Bower [69]; Heylen [70]; Muggia-Sullam [71]

Klein

[78]

Klein

[78]

Klein

[78];

Donaldson

Herdon [91] Alexander

[67]

Feller [40]; Blackburn [41] Goodgame & Fischer [42] Grant [43]; Sax [44]

15]

Gastrointestinal fistulas (PN or EN)

Restrospective studies have shown increased spontaneous closure and reduced mortality with PN or EN as compared to historical series.

Voitk [26]; MacFadyen [27]; Rocchio [26]; Kaminski [29]; Reber [30]; Soeters [24] Thomas [31]; Sitges-Serra [32]; Maclntyre [33]; Rose

Short bowel syndrome (PN)

No randomized studies, but survival without PN exceptional, at least during the adaptation phase. Essential amino acids + glucose vs glucose alone led to increased recovery rate and less need for dialysis. Same regimen as above--no differences.

Wilmore [4]; Tilson [3]

[34]

Renal failure (PN)

Randomized studies comparing nutritional support vs. starvation ethically unacceptable. EN preferred to PN whenever possible because of its physiological benefits; lower cost often cited but difficult to evaluate.

High protein intake of benefit in children with burns.

[92]

Mclntyre [ 10]; Muller [ 11]; Dickinson [9] Saverymuttu [ 19]; Harries [ Rombeau [ 12]

EN preferred to PN whenever possible because of its physiologic benefits; lower cost often cited but difficult to evaluate.

PN should be started 7-10 days preoperatively. Treatment toxicity not adequately evaluated. Potential benefit of EN during radiotherapy or chemotherapy not adequately evaluated.

[79]

Yeung [66]; Moore & Jones Adams [68] Cerra [85]; Bonau [86]; Brennan [87] Askanazi [88] Nordenstrom [89]

PN more effective in malnourished patients submitted to major surgical procedures. No studies in which only EN evaluated.

Abel [59]; Abel [61]; Leonard

[83]

THE AMERICAN JOURNAL OF SURGERY

PN probably effective as supportive treatment in severe pancreatltis. Role as primary treatment not yet defined. Probably effective as supportive treatment. Role as primary treatment not yet defined. More effective in Crohn's disease than in ulcerative colitis, EN not evaluated in ulcerative colitis. Preoperative PN evaluated only in retrospective study. Randomized studies not available-ethically difficult. PN or EN effective as supportive treatment. Role as primary treatment not yet defined, Randomized studies ethically unacceptable. NS mandatory during adaptative period. Preliminary good results with PN have not been confirmed. No EN studies done.

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439

MEGUIDET AL

TABLE V (continued) Summary of the Results of the Use of Parenteral or Enteral Nutrition in Surgical Practice Indications

Liver failure (PN or EN)

Acute respiratory failure (PN or EN)

Results

Author, Reference*

BCAA-enriched PN at least as effective and probably faster recovery than lactulose or neomycin in awaking from encephatopathy. BCAA-PN not different from conventional PN. Data suggest that nutritional support may facilitate weaning from ventilators.

Rossi-Fanelli [66]; Cerra [69]; Gluud [ 73]; Strauss [ 72]; Wahren [71]

Bassili [83] Driver [ 76],

[ 78]

Comments Studies varied in amount of BCAA infused, caloric source, severity of encephalopathy, and endpoint. BCAA-enriched EN of potential benefit in liver disease. No prospective studies in which PN or EN evaluated in patients with acute respiratory failure.

* References from preoperative indications to burn indications are from Meguid MM, Campos AC, Hammond WG. Nutritional support in surgical practice: Part I. Am J Surg 1990; 159:345-58. PN = parenteral nutrition; EN = enteral nutrition; BCAA = branched chain amino acids; NS = nutritional support; I' = increase; ~, = decrease.

probably more rapid than in the control groups. The cumulative trend in rapidity of wake-up favors those patients receiving BCAA mixtures as opposed to those receiving standard treatments (neomycin, lactulose) or placebo. Acute respiratory failure: Driver et al [76] assessed the nutritional status of patients with chronic obstructive pulmonary disease (COPD) who had respiratory failure. Percent of ideal body weight, anthropometrics, and visceral measurements of nutritional status were less than those from a control group of 18 patients without respiratory failure. They concluded that protein-calorie malnutrition should be suspected in patients with COPD and respiratory failure. Pingleton and Eulberg [77] evaluated the nutritional status of 80 consecutive patients admitted to the respiratory intensive care unit with varying etiologies of acute respiratory failure. Body weight of less than 80% of ideal was noted in 24%, and anthropometic measurements of tricep skinfold thickness and midarm muscle circumference were abnormal in almost half the patients. Although poor nutritional status per se did not seem to predispose to a need for mechanical ventilation, malnourished patients who required mechanical ventilation had a significantly higher mortality than did well-nourished patients requiring mechanical ventilation. Furthermore, patients with acute respiratory failure are at risk for worsening nutritional status without appropriate nutritional support. Driver and LeBrun [78] found inadequate nutritional intake in 23 of 26 patients mechanically ventilated for more than 1 week. Harmon et al [79] found similar results in over a 1-year period retrospective study where nutritional assessment of patients with respiratory disease was performed. During the days spent in the intensive care unit, the requirements for energy, protein, and carbohydrate were met in only 70%, 26%, and 51%, respectively. In 19 postoperative patients undergoing mechanical ventilation for respiratory failure, the energy expenditure was 17% above basal energy expenditure as shown by Weissman et al [80]. Patients studied by Roulet et al [81] had a 13% increase in metabolic rate, whereas in a preliminary study, Harmon and Pingleton [82] found energy requirements to range from 29% to 54% above basal energy expenditure in ventilated 440

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patients with COPD. It was concluded that most patients with acute respiratory failure required less than 2,500 calories/day. Only rarely are higher requirements necessary. During a 2-year period, Bassili and Deitel [83] reviewed the "weanability" of patients undergoing mechanical ventilation for more than 3 days. Weaning was accomplished in only 55% of the patients who were receiving an inadequate diet, compared with 93% of the patients with adequate nutritional support. These findings correspond to a retrospective analysis of long-term ventilator-assisted patients by Lorca and Greenbaum [84]. Prospective studies to confirm these data have not yet been reported. Askanazi et al [85] studied the effect of large carbohydrate loads on three patient groups: a protein-caloriedepleted group, a normal metabolic group, and a hypermetabolic group; all three groups showing increases in carbon dioxide production. Only in the hypermetabolic patients was an increase in oxygen consumption seen. Askanazi et al [86] also described a single case in which dyspnea was thought to have originated from administration of parenteral nutrition containing large amounts of glucose. Covelli et al [87] reported three patients receiving intermittent mechanical ventilation because respiratory failure developed due to increased carbon dioxide production within hours after initiation of parenteral nutrition. However, it is not yet clear whether the maintained increases in carbon dioxide production resulting from the long-term high carbohydrate loads of parenteral nutrition are clinically important in patients with respiratory failure. No prospective randomized controlled trials exist that demonstrate an effect of nutritional support in reducing morbidity and mortality in patients with respiratory failure. Despite this, nutritional support is frequently given in such patients when critically ill to maintain or improve nitrogen balance and lean body mass. CONCLUSION Many of the aforementioned disorders are necessarily associated with interruption of the usual oral pathway for nutrition, either from effects of treatment or of the disease, or both. Whereas well-nourished patients can toler-

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ate the combined metabolic insults of both disease and starvation for brief periods, allowing long-term starvation to be added to the stresses of disease and/or treatment is not sensible from a therapeutic standpoint. With the ready availability of modern techniques and personnel (Nutrition Support Team) for nutritional support, protein-calorie malnutrition can be deleted from the list of factors with which the seriously ill patient must cope. Table V summarizes the available evidence as to the benefit of nutritional support to the hospitalized patient and as such constitutes a synopsis of nutritional support in surgical practice. These data indicate that substantial nutritional support, whether as parenteral or enteral nutrition, has little or no direct effect upon the pathogenesis of the various disease entities considered earlier. In pancreatitis, inflammatory bowel disease, fistulas, and trauma of the gastrointestinal tract, the discontinuance of oral intake m a y well have a beneficial effect on the basic disease process; in such instances, the provision of complete nutrition by an alternate route gives the patient an optimal opportunity to marshal host defenses in support of healing. In the short bowel syndrome, parenteral nutrition enables survival by providing a substitute pathway for receipt of needed nutrients. In organ system failure, appropriate nutritional support m a y assist the patient in coping with the abnormal intermediary metabolism resuiting from such failure until satisfactory organ system function returns. Throughout, it seems reasonably clear that the initially malnourished patient is less able to successfully withstand the adverse effects of vigorous therapy a n d / o r severe illness than is the well-nourished individual. Hence, correction of malnutrition, either before initiating therapy whenever possible or concomitant with treatment when necessary, is very likely to be beneficial. Whether the specific treatments directed toward correction of the disease processes will always be able to succeed in the absence of malnutrition, is, of course, another story for another time.

ACKNOWLEDGMENT The authors thank Mrs. Darlene Thompson and Mrs. Debra Spadaro for their diligent editorial assistance.

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