Semi-Elemental Formula or Polymeric Formula: Is There a Better Choice for Enteral Nutrition in Acute Pancreatitis? Randomized Comparative Study  
From the * Gastroenterology and Nutrition
Department, Teaching Hospital, Caen, France; Correspondence: Laurent-Eric Tiengou, MD, Service de Gastroentérologie et Nutrition, Centre Hospitalier Universitaire de Caen, Avenue de la Côte de Nacre, 14033 Caen Cedex, France. Electronic mail may be sent to tiengou-le{at}chu-caen.fr.
Background: Jejunal nutrition is recommended during acute
pancreatitis. The use of semi-elemental formulas presents several theoretical
advantages over polymeric formulas, but their clinical value has been poorly
documented. Our aim was to evaluate in patients with acute pancreatitis the
effect of enteral nutrition by a semi-elemental formula compared with a
polymeric formula. Methods: A randomized prospective pilot study,
stratified according to severity, was performed in 30 consecutive patients
with acute pancreatitis requiring jejunal nutrition. The semi-elemental group
received 35 kcal/kg/d of Peptamen (n = 15), and the polymeric group received
the same quantity of Sondalis-Iso (n = 15). Tolerance was evaluated after 7
days of enteral nutrition (D7) on visual analog scale (VAS), stool frequency,
and 24-hour steatorrhea/creatorrhea. Outcome was evaluated by weight loss,
length of hospital stay, and infection rate. Results: Results were
calculated as mean ± SEM, t-test, or Conventional treatment of acute pancreatitis is based on "resting" of the pancreas by suspending all oral feeding. The concept of pancreatic resting, although its favorable impact on the prognosis of the disease has never been demonstrated, remains part of routine clinical practice because it enables pain relief, whereas premature resumption of oral feeding induces recurrence of pain.1,2 Acute pancreatitis is accompanied by a state of aggression (ie, catabolism under the influence of inflammatory mediators) and is responsible for increased energy expenditure, justifying early nutrition support.3,4 For a long time, the reference nutrition support has been exclusive parenteral nutrition designed to avoid stimulating pancreatic secretion. However, several recent studies have demonstrated the superiority of jejunal nutrition over parenteral nutrition.5–9 Provided the feeding tube is placed in the jejunum, enteral nutrition is well tolerated and reduces the septic complication rate5 and the cost of management.6 Enteral nutrition also decreases the systemic inflammatory response and allows more rapid resolution of pancreatitis compared with parenteral nutrition.2,7 Three of the 4 published randomized trials comparing enteral nutrition vs parenteral nutrition used a semi-elemental nutrition formula (including small peptides and medium-chain triglycerides),5,6,8 whereas the fourth study used a polymeric formula (comprising nonhydrolyzed proteins and long-chain triglycerides).7 Despite the different nutrition formulas used, these 4 studies and a recent meta-analysis9 coherently demonstrated the superiority of enteral administration over parenteral administration. Maintenance of the integrity of the gastrointestinal mucosa by enteral nutrition is supposed to be one of the key factors allowing improvement of the prognosis of acute pancreatitis by decreasing septic complications secondary to bacterial translocation.2,6,7 Nevertheless, bacterial translocation was not proven in humans. Semi-elemental formulas therefore present several theoretical advantages. A semi-elemental formula stimulates pancreatic secretions to a lesser degree than a polymeric formula10 and would therefore decrease the risk of acute episodes of pain after nutrition. Furthermore, in a context of acute pancreatitis, exocrine pancreatic secretions are decreased, and absorption of a semi-elemental formula, which does not require the presence of pancreatic enzymes, would be better than that of a polymeric formula.11 Finally, in animal models, a semi-elemental formula would be able to more effectively maintain the integrity of the intestinal mucosa12 and prevent septic complications due to translocation of gastrointestinal bacteria.13 Despite all of these theoretical advantages, the use of a semi-elemental formula is limited by its cost, which is about 3-fold higher than that of polymeric formulas. It therefore appeared necessary to demonstrate the value of these formulas. The objective of this study was to compare a semi-elemental formula to a polymeric formula in patients with acute pancreatitis in terms of tolerance and the impact on the clinical outcome (length of stay, loss of weight, infectious complications). Our prestudy hypothesis was that semi-elemental formula could lead to a better outcome than polymeric formula.
Patients Over a 1-year period, all patients hospitalized in the Gastroenterology and Nutrition Department of Caen Teaching Hospital for acute pancreatitis requiring jejunal nutrition were assessed before inclusion. They had to be over the age of 18 years and had to give their written informed consent. Exclusion criteria were as follows: edematous acute pancreatitis with a Balthazar score  B, not justifying treatment by enteral nutrition;
hypertriglyceridemia >10 mmol/L on the day of inclusion (D0); failure of
insertion of the nasojejunal tube; and life-threatening intercurrent diseases.
All patients received symptomatic treatment comprising suspension of oral
feeding, gastric aspiration in the case of ileus, IV fluids (40 mL/kg/d +
compensation of gastric aspiration), vitamin B1 and B6
supplements (in alcoholic patients), and analgesics. In accordance with
consensus conference guidelines, antibiotics were not prescribed
systematically but only in the presence of signs of infection after obtaining
bacteriological specimens of the necrotic
fluid.14 After
relieving possible ileus (nasogastric tube withdrawn, resumption of flatus
± stools), a self-propelled nasojejunal tube (Bengmark CH10; Nutricia,
Rueil Malmaison, France) was inserted. This tube has a spiral extremity, which
migrates spontaneously into the jejunum. The objective was to place the tube
beyond the duodenojejunal flexure. When the tube failed to migrate after 48
hours, despite the use of a prokinetic (metoclopramide), another tube (Corflo
CH12; Ansell Medical) was placed, under general anesthesia, by endoscopic
control. Before insertion of nasojejunal tube, some patients received
peripheral parenteral nutrition. This procedure constitutes standard
management of moderate or severe acute pancreatitis in our center. The patient
was included when the nasojejunal tube was in place (D0).
Methods Nutrition objectives in terms of energy intake were 35 kcal/kg of body weight, with 1.5 g of proteins/kg of body weight per day. Enteral nutrition was administered continuously over 18 hours, using a pump. Nutrition intakes were standardized, 500 mL the first day and then gradually increasing (1000 mL the second day, 1500 mL the third day...) to reach nutrition objectives. Isocaloric, isonitrogenous, and isovolumic enteral nutrition solutions were allocated according to randomization after stratification for severity of acute pancreatitis according to Balthazar's score. The semi-elemental group received a semi-elemental formula (Peptamen; Nestlé Clinical Nutrition, Noisiel, France). Peptamen is a balanced isocaloric (1 kcal/mL) formula including 40 g of protein per 1000 kcal. Proteins are hydrolyzed into peptides (1% of free amino acids, 40% of peptides made of <10 amino acids, 46% of peptides of 10–40 amino acids, and 13% of peptides of >40 amino acids). Seventy percent of lipids are in the form of medium-chain triglycerides (11 g of long-chain triglycerides and 26 g of medium-chain triglycerides per 1000 kcal). The polymeric group received a polymeric formula (Sondalis-Iso; Nestlé Clinical Nutrition). This is a balanced isocaloric (1 kcal/mL) polymeric formula comprising 38 g of proteins per 1000 kcal.
Tolerance was evaluated by a form given to each patient. The number of
stools, gastrointestinal pain, and bloating were recorded. Evaluation of
abdominal pain was performed at the beginning and at the end of the study by
means of a visual analog scale (VAS) on D0 and D7, with analysis of the
variation between D0 and D7 (scored as D7-D0). As bloating was difficult to
assess, we only considered the presence or absence of this symptom. We also
studied the number of days on which patients had to use class
Statistics
Patient Characteristics Ninety-eight subjects were admitted to the gastroenterology and nutrition department of Caen Teaching Hospital for acute pancreatitis over a 1-year period. Fifty-six did not require enteral nutrition because Balthazar score was A or B. Six patients were not included because of screening failure and 36 patients were included in the protocol. Six patients were excluded (5 in the polymeric group, 1 in the semi-elemental group) due to avulsion or vomiting of the tube and refusal of insertion of a new tube in 3 cases, development of an early vascular accident on D1 in 1 case, complete refusal of tests on D7 in 1 case, and recurrence of ileus with repeated vomiting on D1 in the last case. These patients were fed by parenteral nutrition. The 30 subjects who completed the protocol were patients hospitalized in a continuous-care department; none of them presented clinical features requiring intensive care management. This series was composed of 24 males and 6 females with a mean age of 46 ± 2 years. Patients were randomized to 2 groups, with stratification according to severity. Fifteen subjects received enteral nutrition with a semi-elemental formula (semi-elemental group), and 15 subjects received enteral nutrition with a polymeric formula (polymeric group). As shown in Table I, the 2 groups were comparable on inclusion in terms of age, gender, Balthazar score, etiology of pancreatitis, visual analog pain score, and also in terms of the following laboratory parameters: C-reactive protein (CRT), serum amylase, and serum albumin. Initial management was identical in the 2 groups. Before insertion of the nasojejunal tube, half the patients received peripheral parenteral nutrition (7/15 in semi-elemental and 8/15 in polymeric; NS) for 8 ± 1 day. The number of days of ileus was comparable (2.4 ± 0.5 vs 2.9 ± 0.7; NS), the total number of days of fasting before insertion of the nasojejunal tube was also comparable (7.5 ± 0.9 vs 8.6 ± 1.0; NS). A self-propelled tube was used in 24 out of 30 cases, with a similar proportion in each group (11 out of 15 vs 13 out of 15; NS).
Tolerance and Absorption of Enteral Nutrition
Clinical Outcome
One infectious complication was observed in the semi-elemental group vs 3 in the polymeric group (NS). All infections were documented by taking samples of pancreatic necrosis in 3 cases and by urinary culture in 1 case. All cases of sepsis were controlled by antibiotics. There were no cases of multiorgan failure and no transfers to the intensive care unit. Only 1 death was observed in this series of 30 subjects, unrelated to acute pancreatitis, in a patient with high-grade intestinal lymphoma who died from complications of bowel obstruction 46 days after the end of the protocol. No significant difference was demonstrated between the 2 nutrition formulas in terms of laboratory test results. The time course of the biochemical parameters considered was similar in the 2 arms, with an identical decrease of CRP and serum amylase and a similar elevation of serum albumin between D0 and D7 in the 2 groups (Table IV). Serum procalcitonin was not shown to be clinically useful in our study, as all but 2 of the 60 values were normal. Follow-up abdominal CT scan performed on D7 showed a favorable course in all patients. No difference in the course of CT findings was demonstrated between the 2 nutrition formulas.
To our knowledge, no published study has compared these 2 modalities of enteral nutrition in the context of acute pancreatitis. The clinical course of pancreatitis, weight loss, and length of hospital stay seems to be an objective parameter suggesting the superiority of the semi-elemental formula over the polymeric formula. However, our study did not demonstrate any significant difference for the other items studied. In terms of tolerance and gastrointestinal acceptability of enteral nutrition during acute pancreatitis, we can globally conclude on the equivalence of the 2 nutrition formulas. This good safety is mainly due to the fact that both formulas were very well absorbed by the gastrointestinal tract. The 24-hour stool number and stool weights were low, and values for steatorrhea and creatorrhea were well below pathologic values. There is therefore no disadvantage for the use of a polymeric formula, which does not induce more abdominal pain, diarrhea, or bloating. Evaluation of the global tolerance of the nutrition was excellent, with no significant difference between the 2 groups. These results differed from what we had expected, as acute pancreatitis induces a reduction of exocrine pancreatic secretions theoretically able to reduce the capacities of absorption of polymeric formulas.17 However, interpretation of our results must take into account the fact that our patients, although sometimes presenting with signs of necrotic acute pancreatitis, did not show any clinical or laboratory features justifying admission to the intensive care unit. They therefore constitute a subgroup of patients with moderately severe necrotic acute pancreatitis. Another study has suggested that pancreatic exocrine secretion is preserved in the case of moderate pancreatitis.18 These results are similar to those obtained in other pathologic settings (Crohn's disease, short bowel syndrome) in which the theoretical advantages in favor of a semi-elemental formula were not demonstrated in clinical practice.19,20 Jejunal nutrition allowed a favorable clinical course of acute pancreatitis in the 2 groups. Regression of the lesions of acute pancreatitis was obtained regardless of the type of nutrition used, and no major complications were observed. However, our study demonstrated differences between the 2 types of nutrition formulas. Semi-elemental nutrition is accompanied by more favorable prognostic criteria. For example, a decreased weight loss was observed in patients receiving the semi-elemental formula. As the protein and caloric intakes were comparable in the 2 groups, this difference is probably due to higher energy expenditure in the polymeric group, reflecting a less well-controlled catabolic situation. This hypothesis is consistent with the longer length of hospital stay in the polymeric group. This difference is not due to the time to inclusion, as this interval was similar in the 2 arms of the study, but is clearly related to the length of stay after initiation of enteral nutrition. The semi-elemental formula also appeared to be associated with a small number of infections, although no statistically significant difference was observed in our study. The relatively moderate severity of pancreatitis in our study probably tended to decrease the frequency and severity of sepsis. No formal pathophysiological explanation can be provided for the more favorable clinical course observed in the group treated with the semi-elemental formula. According to the literature, we can propose the hypothesis that trophicity of the intestinal mucosa is better maintained in this group,5–7 leading to a decreased risk of bacterial translocation, explaining the more favorable clinical course in this group. But at present time, this theory cannot be documented with clinical data in humans. No definite conclusions can be drawn due to the small sample size, corresponding to a highly selected population. Our results could be confirmed by a study on a larger population presenting more severe forms of acute pancreatitis, using the prevalence of gastrointestinal-derived infections as the primary endpoint. The use of nasogastric feeding, recently proposed,21 could be also evaluated in further studies. In conclusion, our study confirmed the good tolerance of jejunal nutrition in acute pancreatitis. The 2 types of nutrition formula were very well absorbed, were accompanied by few gastrointestinal symptoms, and allowed resolution of acute pancreatitis. Our results also suggest that semi-elemental nutrition could ensure a more favorable clinical outcome than nutrition with a polymeric formula. Received for publication November 12, 2004. Accepted for publication August 4, 2005.
Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 1,
1-5 (2006) This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
|
 |
|
2.
Patients of the 2 groups were comparable in terms of age, gender, and
severity. Tolerance was good in both groups (semi-elemental vs
polymeric: VAS, 7.4 ± 0.6 vs 7.1 ± 0.6, not significant
(NS); number of stools per 24 hours, 1.7 ± 0.4 vs 1.8 ±
0.4, NS). Steatorrhea and creatorrhea were lower than normal in both groups.
In semi-elemental group, the length of hospital stay was shorter (23 ±
2 vs 27 ± 1, p = .006) and weight loss was less
marked (1 ± 1 vs 2 ± 0, p = .01). One patient
in semi-elemental group and 3 patients in polymeric group developed an
infection (NS). Conclusions: Semi-elemental and polymeric nutrition
are very well tolerated in patients with acute pancreatitis. Nutrition with a
semi-elemental formula supports the hypothesis of a more favorable clinical
course than nutrition with a polymeric formula, but this conclusion needs to
be established in larger adequately powered clinical trials. 
Top
PATIENTS AND METHODS
RESULTS
D).
